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DNA and RNA error checking and repair, amazing evidence of design

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DNA and RNA error checking and  repair, amazing evidence of design

http://reasonandscience.heavenforum.org/t2043-dna-and-rna-error-checking-and-repair-amazing-evidence-of-design

Jon Lieff MD:

http://jonlieffmd.com/blog/dna-proofreading-correcting-mutations-during-replication-cellullar-self-directed-engineering
During replication, nucleotides, which compose DNA, are copied. When E coli makes a copy of its DNA, it makes approximately one mistake for every billion new nucleotides. It can copy about 2000 letters per second, finishing the entire replication process in less than an hour.  Compared to human engineering, this error rate is amazingly lowcoli makes so few errors because DNA is proofread in multiple ways. An enzyme, DNA polymerase, moves along the DNA strands to start copying the code from each strand of DNA.  This process has an error rate of about one in 100,000: rather high.  When an error occurs, though, DNA polymerase senses the irregularity as a distortion of the new DNA’s structure, and stops what it is doing. How a protein can sense this is not clear. Other molecules then come to fix the mistake, removing the mistaken nucleotide base and replacing it with the correct one. After correction, the polymerase proceeds. This correction mechanism increases the accuracy 100 to 1000 times.


A Second Round of Proofreading

There are still some errors, however, that escape the previous mechanism. For those, three other complex proteins go over the newly copied DNA sequence.  The first protein, called MutS (for mutator), senses a distortion in the helix shape of the new DNA and binds to the region with the mistaken nucleotides. The second protein, MutL, senses that its brother S is attached and brings a third protein over and attaches the two.  The third molecule actually cuts the mistake on both sides.  The three proteins then tag the incorrect section with a methyl group. Meanwhile, another partial strand of DNA is being created for the region in question, and another set of proteins cut out the exact amount of DNA needed to fill the gap.  With both the mistaken piece and newly minted correct piece present, yet another protein determines which is the correct one by way of the methyl tag. That is, the correct one does not have the methyl tag on it.  This new, correct section is then brought over and added to the original DNA strand. This second proofreading is itself 99% efficient and increases the overall accuracy of replication by another 100 times.
  
Multiple Sensors
There are multiple places where a protein “senses” what needs to be done.  The computer-like sensing of the original mistake, cannot be directed by the original DNA. Clearly, there are other sources of decision-making in a cell. While DNA’s “quality control” is extremely complex in E.Coli, the same process is even more complex in the human cell. Human cells contain many different polymerases and many other enzymes to cut and mend mistakes.  There are even different Mut-type systems that, along with other proofreading, render human DNA replication incredibly accurate. Very recent research has shown some of the complex mechanisms of the MutL family of mutation correction molecules.  It shows that an energy molecule ATP stimulates the process whereby MutL cuts the DNA around the error.  There are two grooves in the MutL molecule, one for ATP and one for the DNA strand. When ATP binds to MutL it changes the protein’s shape which allows the cutting to occur.  In humans when MutL is not functioning properly it is know to cause cancer.

While mutations help determine evolutionary variety, we still don’t know how these very elaborate and multi-layered quality controls came about and how they are directed.  Is it possible for  DNA to directed its own editing?  Somehow, these processes know which are appropriate DNA sequences and which are not. 

Cellular Repair Capabilities. 20
First, then, all cells from bacteria to man possess a truly astonishing array of repair systems which serve to remove accidental and stochastic sources of mutation. Multiple levels of proofreading mechanisms recognize and remove errors that inevitably occur during DNA replication. These proofreading systems are capable of distinguishing between newly synthesized and parental strands of the DNA double helix, so they operate efficiently to rectify rather than fix the results of accidental misincorporations of the wrong nucleotide. Other systems scan non-replicating DNA for chemical changes that  could lead to miscoding and remove modified nucleotides, while additional functions monitor the pools of precursors and remove potentially mutagenic contaminants. In anticipation of chemical and physical insults to the genome, such as alkylating agents and ultraviolet radiation,
additional repair systems are encoded in the genome and can be induced to correct damage when it occurs. It has been a surprise to learn how thoroughly cells protect themselves against precisely the kinds of accidental genetic change that, according to conventional theory, are the sources of evolutionary variability. By virtue of their proofreading and repair systems, living cells are not passive victims of the random forces of chemistry and physics. They devote large resources to suppressing random genetic variation and have the capacity to set the level of background localized mutability by adjusting the activity of their repair systems.



5ʹ => 3ʹ polymerization 1 in 100.000
3ʹ => 5ʹ exonucleolytic proofreading 1 in 100
Strand-directed mismatch repair 1 in 1000
Combined 1 in 10.000.000.000

Maintaining the genetic stability that an organism needs for its survival requires not only an extremely accurate mechanism for replicating DNA, but also mechanisms for repairing the many accidental lesions that occur continually in DNA.

DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a base missing from the backbone of DNA, or a chemically changed base. Naturally occurring DNA damages arise more than 60,000 times per day per mammalian cell.   DNA damage appears to be a fundamental problem for life. DNA damages are a major primary cause of cancer. DNA damages give rise to mutations and epimutations. The mutations, if not corrected,  would be propagated throughout subsequent cell generations. Such a high rate of random changes in the DNA sequence would have disastrous consequences for an organism

Different pathways for DNA repair exists, 

Nucleotide excision repair (NER),  
Base excision repair (BER),  
DNA mismatch repair (MMR),  
Repair through alkyltransferase-like proteins (ATLs) amongst others.

Its evident that the repair mechanism is essential for the cell to survive. It could not have evolved after life arose, but must have come into existence before. The mechanism is highly complex and elaborated, as consequence, the design inference is justified and seems to be the best way to explain its existence.

Base excision repair (BER)  involves a category of enzymes  known as  DNA-N-glycosylases.

One example of DNA's  automatic error-correction utilities are enough to stagger the imagination.  There are dozens of repair mechanisms to shield our genetic code from damage; one of them was portrayed in Nature  in terms that should inspire awe.

From Nature's article :
Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA 11

How DNA repair proteins distinguish between the rare sites of damage and the vast expanse of normal DNA is poorly understood. Recognizing the mutagenic lesion 8-oxoguanine (oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G).  The X-ray structure of the trapped complex features a target G nucleobase extruded from the DNA helix but denied insertion into the lesion recognition pocket of the enzyme. Free energy difference calculations show that both attractive and repulsive interactions have an important role in the preferential binding of oxoG compared with G to the active site. The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site.

Of the four bases in DNA (C, G, A, and T) cytosine or C is always supposed to pair with guanine, G, and adenine, A, is always supposed to pair with thymine, T.  The enzyme studied by Banerjee et al. in Nature is one of a host of molecular machines called BER glycosylases; this one is called human oxoG glycosylase repair enzyme (hOGG1), and it is specialized for finding a particular type of error: an oxidized G base (guanine).  Oxidation damage can be caused by exposure to ionizing radiation (like sunburn) or free radicals roaming around in the cell nucleus.  The normal G becomes oxoG, making it very slightly out of shape.  There might be one in a million of these on a DNA strand.  While it seems like a minor typo, it can actually cause the translation machinery to insert the wrong amino acid into a protein, with disastrous results, such as colorectal cancer.  12

The machine latches onto the DNA double helix and works its way down the strand, feeling every base on the way.  As it proceeds, it kinks the DNA strand into a sharp angle.  It is built to ignore the T and A bases, but whenever it feels a C, it knows there is supposed to be a G attached.  The machine has precision contact points for C and G.  When the C engages, the base paired to it is flipped up out of the helix into a slot inside the enzyme that is finely crafted to mate with a pure, clean G.  If all is well, it flips the G back into the DNA helix and moves on.  If the base is an oxoG, however, that base gets flipped into another slot further inside, where powerful forces yank the errant base out of the strand so that other machines can insert the correct one.

Now this is all wonderful stuff so far, but as with many things in living cells, the true wonder is in the details.  The thermodynamic energy differences between G and oxoG are extremely slight – oxoG contains only one extra atom of oxygen – and yet this machine is able to discriminate between them to high levels of accuracy.

The author, David, says in the Nature article :

Structural biology:  DNA search and rescue
DNA-repair enzymes amaze us with their ability to search through vast tracts of DNA to find subtle anomalies in the structure. The human repair enzyme 8-oxoguanine glycosylase (hOGG1) is particularly impressive in this regard because it efficiently removes 8-oxoguanine (oxoG), a damaged guanine (G) base containing an extra oxygen atom, and ignores undamaged bases.

Natural selection cannot act without accurate replication, yet the protein machinery for the level of accuracy required is itself built by the very genetic code it is designed to protect.  Thats a catch22 situation.  It would have been challenging enough to explain accurate transcription and translation alone by natural means, but as consequence of UV radiation, it  would have quickly been destroyed through accumulation of errors.  So accurate replication and proofreading are required for the origin of life. How on earth could proofreading enzymes emerge, especially with this degree of fidelity, when they depend on the very information that they are designed to protect?  Think about it....  This is one more prima facie example of chicken and egg situation. What is the alternative explanation to design ? Proofreading DNA by chance ?  And a complex suite of translation machinery without a designer?

I  enjoy to learn about  the wonder of these incredible mechanisms.  If the apostle Paul could understand that creation demands a Creator as he wrote in Romans chapter one 18, how much more we today with all the revelations about cell biology and molecular machines?  

http://reasonandscience.heavenforum.org/t2043-dna-repair#3475


DNA repair mechanisms, designed with special care in order to provide integrity of DNA, and  essential for living organisms of all domains.

In fact, Nature uses special proteins called ‘proofreading enzymes’ to prevent the occurrence of slight changes in sequence when DNA replicates. The enzymes that copy DNA to DNA, or DNA to RNA, are indeed very clever. They can sense at several stages during synthesis whether anything is going wrong; for example, if they have added or are about to add the wrong base, according to the Watson–Crick rules of pairing. Also, there are ‘repair’ enzymes that go around correcting occasional mistakes of copying or ‘mismatches’. Thus, Nature goes to great lengths to avoid errors in the copying of DNA, even though the atoms in the DNA structure are actually quite tolerant of mismatch pairings. These enzymes are extremely efficient in doing their job, yet no one knows exactly how they work.

The evidence through DNA repair 
1. Broken or mismatched DNA strands can lead to serious diseases and even death.  It is essential that DNA damage be recognized and repaired quickly. 
2. A team at Rockefeller University and Harvard Medical School that found two essential proteins that act like “molecular tailors” that can snip out an error and sew it back up with the correct molecules. 
3. These proteins, FANC1 and FANCD2, repair inter-strand cross-links, “one of the most lethal types of DNA damage.”  This problem “occurs when the two strands of the double helix are linked together, blocking replication and transcription.” 
4. Each of your cells is likely to get 10 alarm calls a day for inter-strand cross-links.
5. The   FANC1 and FANCD2 link together and join other members of the repair pathway, and are intimately involved in the excision and insertion steps.
6. One repair operation requires 13 protein parts. 
7. “If any one of the 13 proteins in this pathway is damaged, the result is Fanconi anemia, a blood disorder that leads to bone marrow failure and leukemia, among other cancers, as well as many physiological defects.”
a. “Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.” 
8. In the scientific paper and press release nor Darwin nor the possible way of how this tightly-integrated system might have evolved was mentioned.
9. The absolute necessity of FANC1 and FANCD2 are very much obvious from this discovery not only in one species but in all that has DNA. Their crucial role for survival of the species is undismissable. 
10. Their must have existed as perfectly functional units from the time of appearance of any species on this planet otherwise existence would be not possible.
11. This implies creation what further implies that God necessarily exists.

Reference:
1.  Knipscheer et al, “The Fanconi Anemia Pathway Promotes Replication-Dependent DNA Interstrand Cross-Link Repair,” Science, 18 December 2009: Vol. 326. no. 5960, pp. 1698-1701, DOI: 10.1126/science.1182372.

Argument from detection/correction codes
1. The GCL binary representation makes possible the existence of error detection/correction codes that operate along the strands of DNA.
2. “An error-control mechanism implies the organization of the redundancy in a mathematically structured way,” and “the genetic code exhibits a strong mathematical structure that is difficult to put in relation with biological advantages other than error correction.”
3. A peculiar and unique mathematical model accounts for the key properties of the genetic code that exhibits symmetry, organized redundancy, and a mathematical structure crucial for the existence of error-coding techniques operating along the DNA strands.
4. The DNA data tested using this model gave a strong indication that error-coding techniques do exist.
5. Such a wonderful design indicates purposeful creation that further indicates the existence of God.
6. God exists.

The evidence of Rad51 
1. The scientists from the Lawrence Berkeley National Lab in their essay: “Safeguarding genome integrity through extraordinary DNA repair,” write:
Homologous recombination is a complex mechanism with multiple steps, but also with many points of regulation to insure accurate recombination at every stage.  This could be why this method has been favored during evolution.  The machinery that relocalizes the damaged DNA before loading Rad51 might have evolved because the consequences of not having it would be terrible.
2. If evolution is a chance process with no goal or purpose, it would not care if something emerges or not.  How can a mindless process “favor” a method?  How would a mindless process “know” that the consequences of not having something would be terrible?  How would that motivate a non-mind to produce machinery and complex mechanisms to avoid terrible consequences?
3. Thus instead of saying ‘Rad51 might have evolved’ it is clear that Rad51 was designed by an intelligent designer since without such a complex mechanism with multiple steps with many points of regulation to insure accurate recombination at every stage, life could not exist.
4. The ability of Rad51 that has the ability of extraordinary DNA repair proofs the existence of an intelligent designer all men call God.
5. God exists.




DNA repair

http://reasonandscience.heavenforum.org/t2043-dna-repair?highlight=dna+repair



DNA repair mechanisms make no sense in an evolutionary presupposition. Error correction requires error detection, and that requires the detection process to be able to compare the DNA as it is to the way it ought to be. DNA repair is regarded as one of the essential events in all life forms. 18 The stability of the genome is essential for the proper function and survival of all organisms. DNA damage is very frequent and appears to be a fundamental problem for life. DNA damage can trigger the development of cancer, and accelerate aging. 19

Kunkel, T.A., DNA Replication Fidelity, J. Biological Chemistry 279:16895–16898, 23 April 2004.

This machinery keeps the error rate down to less than one error per 100 million letters

Maintaining the genetic stability that an organism needs for its survival requires not only an extremely accurate mechanism for replicating DNA, but also mechanisms for repairing the many accidental lesions that occur continually in DNA. Most such spontaneous changes in DNA are temporary because they are immediately corrected by a set of processes that are collectively called DNA repair. Of the thousands of random changes created every day in the DNA of a human cell by heat, metabolic accidents, radiation of various sorts, and exposure to substances in the environment, only a few accumulate as mutations in the DNA sequence. For example, we now know that fewer than one in 1000 accidental base changes in DNA results in a permanent mutation; the rest are eliminated with remarkable efficiency by DNA repair. The importance of DNA repair is evident from the large investment that cells make in DNA repair enzymes. For example, analysis of the genomes of bacteria and yeasts has revealed that several percent of the coding capacity of these organisms is devoted solely to DNA repair functions.

Without DNA repair, spontaneous DNA damage would rapidly change DNA sequences

Although DNA is a highly stable material, as required for the storage of genetic information, it is a complex organic molecule that is susceptible, even under normal cell conditions, to spontaneous changes that would lead to mutations if left unrepaired.

DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a base missing from the backbone of DNA, or a chemically changed base. 15
Naturally occurring DNA damages arise more than 60,000 times per day per mammalian cell.

DNA damage appears to be a fundamental problem for life. DNA damages are a major primary cause of cancer. DNA damages give rise to mutations and epimutations that, by a process of natural selection, can cause progression to cancer. 16

Different pathways to repair DNA

DNA repair mechanisms fall into 2 categories

– Repair of damaged bases
– Repair of incorrectly basepaired bases during replication

Cells have multiple pathways to repair their DNA using different enzymes that act upon different kinds of lesions.

At least four excision repair pathways exist to repair single stranded DNA damage:

Nucleotide excision repair (NER)
Base excision repair (BER)
DNA mismatch repair (MMR)
Repair through alkyltransferase-like proteins (ATLs)


In most cases, DNA repair is a multi-step process

– 1. An irregularity in DNA structure is detected
– 2. The abnormal DNA is removed
– 3. Normal DNA is synthesized

DNA bases are also occasionally damaged by an encounter with reactive metabolites produced in the cell (including reactive forms of oxygen) or by exposure to chemicals in the environment. Likewise, ultraviolet radiation from the sun can produce a covalent Iinkage between two adjacent pyrimidine bases in DNA to form, for example, thymine dimers This type of damage occurs in the DNA of cells exposed to ultraviolet or radiation(as in sunlight) A similar dimer will form between any two neighboring pyrimidine bases ( C or T residues ) in DNA. ( see below )

If left uncorrected when the DNA is replicated, most of these changes would be expected to lead either to the deletion of one or more base pairs or to a base-pair substitution in the daughter DNA chain. ( see below ) The mutations would then be propagated throughout subsequent cell generations. Such a high rate of random changes in the DNA sequence would have disastrous consequences for an organism

Its evident that the repair mechanism is essential for the cell to survive. It could not have evolved after life arose, but must have come into existence before. The mechanism is highly complex and elaborated, as consequence, the design inference is justified and seems to be the best way to explain its existence.

The DNA double helix is readily repaired

The double-helical structure of DNA is ideally suited for repair because it carries two separate copies of all the genetic information-one in each of its two strands. Thus, when one strand is damaged, the complementary strand retains an intact copy of the same information, and this copy is generally used to restore the correct nucleotide sequences to the damaged strand. An indication of the importance of a double-stranded helix to the safe storage of genetic information is that all cells use it; only a few small viruses use single stranded DNA or RNA as their genetic material. The types of repair processes described in this section cannot operate on such nucleic acids, and once damaged, the chance of a permanent nucleotide change occurring in these singlestranded genomes of viruses is thus very high. It seems that only organisms with tiny genomes (and therefore tiny targets for DNA damage) can afford to encode their genetic information in any molecule other than a DNA double helix.Below shows  two of the most common pathways. In both, the damage is excised, the original DNA sequence is restored by a DNA polymerase that uses the undamaged strand as its template, and a remaining break in the double helix is sealed by DNA ligase.

DNA ligase.

The reaction catalyzed by DNA ligase. This enzyme seals a broken phosphodiester bond. As shown, DNA ligase uses a molecule of ATP to activate the 5' end at the nick    (step 1 ) before forming the new bond (step 2). In this way, the energetically unfavorable nick-sealing reaction is driven by being coupled to the energetically favorable
process of ATP hydrolysis.

The main two pathways differ in the way in which they remove the damage from DNA. The first pathway, called

Base excision repair (BER) 9

It involves a battery of enzymes called DNA glycosylases, each of which can recognize a specific tlpe of altered base in DNA and catalyze its hydrolltic removal. There are at least six types of these enzymes, including those that remove deaminated Cs, deaminated As, different types of alkylated or oxidized bases, bases with opened rings, and bases in which a carbon-carbon double bond has been accidentally converted to a carbon-carbon single bond.

How is an altered base detected within the context of the double helix? A key step is an enzyme-mediated "flipping-out" of the altered nucleotide from the helix, which allows the DNA glycosylase to probe all faces of the base for damage ( see above image ) It is thought that these enzymes travel along DNA using base-flipping to evaluate the status of each base. Once an enzyme finds the damaged base that it recognizes, it removes the base from its sugar. The "missing tooth" created by DNA glycosylase action is recognized by an enzyme called AP endonuclease (AP for apurinic or apyrimidinic, endo to signify that the nuclease cleaves within the polynucleotide chain), which cuts the phosphodiester backbone, after which the damage is removed and the resulting gap repaired ( see figure below ) Depurination, which is by far the most frequent rype of damage suffered by DNA, also leaves a deoxyribose sugar with a missing base. Depurinations are directly repaired beginning with AP endonuclease.  

While the BER pathway can recognize specific non-bulky lesions in DNA, it can correct only damaged bases that are removed by specific glycosylases. Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs. 2

Molecular lesion A molecular lesion or point lesion is damage to the structure of a biological molecule such as DNA, enzymes, or proteins that results in reduction or absence of normal function or, in rare cases, the gain of a new function. Lesions in DNA consist of breaks and other changes in the chemical structure of the helix (see types of DNA lesions) while lesions in proteins consist of both broken bonds and improper folding of the amino acid chain. 6

DNA-N-glycosylases

Base excision repair (BER)  involves a category of enzymes  known as  DNA-N-glycosylases  These enzymes can recognize a single damaged base and cleave the bond between it and the sugar in the DNA removes one base, excises several around it, and replaces with several new bases using Pol adding to 3’ ends then ligase attaching to 5’ end

DNA glycosylases  are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond. Glycosylases were first discovered in bacteria, and have since been found in all kingdoms of life. 8

One example of DNA's  automatic error-correction utilities are enough to stagger the imagination.  There are dozens of repair mechanisms to shield our genetic code from damage; one of them was portrayed in Nature  in terms that should inspire awe. 10

How do DNA-repair enzymes find aberrant nucleotides among the myriad of normal ones?
One enzyme has been caught in the act of checking for damage, providing clues to its quality-control process.

From Nature's article :
Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA 11

How DNA repair proteins distinguish between the rare sites of damage and the vast expanse of normal DNA is poorly understood. Recognizing the mutagenic lesion 8-oxoguanine (oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G).  The X-ray structure of the trapped complex features a target G nucleobase extruded from the DNA helix but denied insertion into the lesion recognition pocket of the enzyme. Free energy difference calculations show that both attractive and repulsive interactions have an important role in the preferential binding of oxoG compared with G to the active site. The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site.

Of the four bases in DNA (C, G, A, and T) cytosine or C is always supposed to pair with guanine, G, and adenine, A, is always supposed to pair with thymine, T.  The enzyme studied by Banerjee et al. in Nature is one of a host of molecular machines called BER glycosylases; this one is called human oxoG glycosylase repair enzyme (hOGG1), and it is specialized for finding a particular type of error: an oxidized G base (guanine).  Oxidation damage can be caused by exposure to ionizing radiation (like sunburn) or free radicals roaming around in the cell nucleus.  The normal G becomes oxoG, making it very slightly out of shape.  There might be one in a million of these on a DNA strand.  While it seems like a minor typo, it can actually cause the translation machinery to insert the wrong amino acid into a protein, with disastrous results, such as colorectal cancer.  12

The machine latches onto the DNA double helix and works its way down the strand, feeling every base on the way.  As it proceeds, it kinks the DNA strand into a sharp angle.  It is built to ignore the T and A bases, but whenever it feels a C, it knows there is supposed to be a G attached.  The machine has precision contact points for C and G.  When the C engages, the base paired to it is flipped up out of the helix into a slot inside the enzyme that is finely crafted to mate with a pure, clean G.  If all is well, it flips the G back into the DNA helix and moves on.  If the base is an oxoG, however, that base gets flipped into another slot further inside, where powerful forces yank the errant base out of the strand so that other machines can insert the correct one.

Now this is all wonderful stuff so far, but as with many things in living cells, the true wonder is in the details.  The thermodynamic energy differences between G and oxoG are extremely slight – oxoG contains only one extra atom of oxygen – and yet this machine is able to discriminate between them to high levels of accuracy.

The author, David, says in the Nature article :

Structural biology:  DNA search and rescue

DNA-repair enzymes amaze us with their ability to search through vast tracts of DNA to find subtle anomalies in the structure. The human repair enzyme 8-oxoguanine glycosylase (hOGG1) is particularly impressive in this regard because it efficiently removes 8-oxoguanine (oxoG), a damaged guanine (G) base containing an extra oxygen atom, and ignores undamaged bases.

The team led by Anirban Banerjee of Harvard, using a clever new stop-action method of imaging, caught this little enzyme in the act of binding to a bad guanine, helping scientists visualize how the machinery works. Some other amazing details are mentioned about this molecular proofreader. It checks every C-G pair, but slips right past the A-T pairs.  The enzyme, “much like a train that stops only at certain locations,” pauses at each C and, better than any railcar conductor inspecting each ticket, flips up the G to validate it.  Unless it conforms to the slot perfectly – even though G and oxoG differ in their match by only one hydrogen bond – it is ejected like a freeloader in a Pullman car and tossed out into the desert.  David elaborates:

Calculations of differences in free energy indicate that both favourable and unfavourable interactions lead to preferential binding of oxoG over G in the oxoG-recognition pocket, and of G over oxoG in the alternative site.  This structure [the image resolved by the scientific team] captures an intermediate that forms in the process of finding oxoG, and illustrates that the damaged base must pass through a series of ‘gates’, or checkpoints, within the enzyme; only oxoG satisfies the requirements for admission to the damage-specific pocket, where it will be clipped from the DNA.  Other bases (C, A and T) may be rejected outright without extrusion from the helix because hOGG1 scrutinizes both bases in each pair, and only bases opposite a C will be examined more closely.

Natural selection cannot act without accurate replication, yet the protein machinery for the level of accuracy required is itself built by the very genetic code it is designed to protect.  Thats a catch22 situation.  It would have been challenging enough to explain accurate transcription and translation alone by natural means, but as consequence of UV radiation, it  would have quickly been destroyed through accumulation of errors.  So accurate replication and proofreading are required for the origin of life. How on earth could proofreading enzymes emerge, especially with this degree of fidelity, when they depend on the very information that they are designed to protect?  Think about it....  This is one more prima facie example of chicken and egg situation. What is the alternative explanation to design ? Proofreading  DNA by chance ?  And a complex suite of translation machinery without a designer?  

I  enjoy to learn about  the wonder of these incredible mechanisms.  If the apostle Paul could understand that creation demands a Creator as he wrote in Romans chapter one 18, how much more we today with all the revelations about cell biology and molecular machines?
 


Since the editing machinery itself requires proper proofreading and editing during its manufacturing, how would the information for the machinery be transmitted accurately before the machinery was in place and working properly? Lest it be argued that the accuracy could be achieved stepwise through selection, note that a high degree of accuracy is needed to prevent ‘error catastrophe’ in the first place—from the accumulation of ‘noise’ in the form of junk proteins specified by the damaged DNA. 18



Depending on the species, this repair system can eliminate  abnormal bases such as Uracil; Thymine dimers 3-methyladenine; 7-methylguanine


14

Since many mutations are deleterious, DNA repair systems  are vital to the survival of all organisms

Living cells contain several DNA repair systems that can fix different type of DNA alterations



Nucleotide excision repair (NER)

Nucleotide excision repair is a DNA repair mechanism.   DNA damage occurs constantly because of chemicals (i.e. intercalating agents), radiation and other mutagens.


Nucleotide excision repair (NER) is a highly conserved DNA repair mechanism.
NER systems recognize the damaged DNA strand, cleave it on both sides of the lesion, remove and newly synthesize the fragment. UvrB is a central component of the bacterial NER system participating in damage recognition, strand excision and repair synthesis.[/b] We have solved the crystal structure of UvrB in the apo and the ATP-bound forms. UvrB contains two domains related in structure to helicases, and two additional domains unique to repair proteins. The structure contains all elements of an intact helicase, and is evidence that UvrB utilizes ATP hydrolysis to move along the DNA to probe for damage. The location of conserved residues and structural comparisons allow us to predict the path of the DNA and suggest that the tight preincision complex of UvrB and the damaged DNA is formed by insertion of a flexible β-hairpin between the two DNA strands. 3

DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including chemicals but also ultraviolet (UV) light from the sun. Nucleotide excision repair (NER) is a particularly important mechanism by which the cell can prevent unwanted mutations by removing the vast majority of UV-induced DNA damage (mostly in the form of thymine dimers and 6-4-photoproducts). The importance of this repair mechanism is evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins including Xeroderma pigmentosum and Cockayne's syndrome. While the base excision repair machinery can recognize specific lesions in the DNA and can correct only damaged bases that can be removed by a specific glycosylase, the nucleotide excision repair enzymes recognize bulky distortions in the shape of the DNA double helix. Recognition of these distortions leads to the removal of a short single-stranded DNA segment that includes the lesion, creating a single-strand gap in the DNA, which is subsequently filled in by DNA polymerase, which uses the undamaged strand as a template. NER can be divided into two subpathways (Global genomic NER and Transcription coupled NER) that differ only in their recognition of helix-distorting DNA damage. 4

Nucleotide excision repair (NER)   is a particularly important excision mechanism that removes DNA damage induced by ultraviolet light (UV). 2UV DNA damage results in bulky DNA adducts - these adducts are mostly thymine dimers and 6,4-photoproducts. Recognition of the damage leads to removal of a short single-stranded DNA segment that contains the lesion. The undamaged single-stranded DNA remains and DNA polymerase uses it as a template to synthesize a short complementary sequence. Final ligation to complete NER and form a double stranded DNA is carried out by DNA ligase. NER can be divided into two subpathways: global genomic NER (GG-NER) and transcription coupled NER (TC-NER). The two subpathways differ in how they recognize DNA damage but they share the same process for lesion incision, repair, and ligation.

The importance of NER is evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins. Xeroderma pigmentosum and Cockayne's syndrome are two examples of NER associated diseases.

Maintaining genomic integrity is essential for living organisms. NER is a major pathway allowing the removal of lesions which would otherwise accumulate and endanger the health of the affected organism.  5

Nucleotide excision repair (NER) is a mechanism to recognize and repair bulky DNA damage caused by compounds, environmental carcinogens, and exposure to UV-light. In humans hereditary defects in the NER pathway are linked to at least three diseases: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). The repair of damaged DNA involves at least 30 polypeptides within two different sub-pathways of NER known as transcription-coupled repair (TCR-NER) and global genome repair (GGR-NER). TCR refers to the expedited repair of lesions located in the actively transcribed strand of genes by RNA polymerase II (RNAP II). In GGR-NER the first step of damage recognition involves XPC-hHR23B complex together with XPE complex (in prokaryotes, uvrAB complex). The following steps of GGR-NER and TCR-NER are similar.





1


1) http://www.genome.jp/dbget-bin/www_bget?ko03420
2) http://en.wikipedia.org/wiki/Nucleotide_excision_repair
3) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171753/pdf/006899.pdf
4) http://bioisolutions.blogspot.com.br/2008/04/ner-pathway.html
5) http://intelligent-sequences.blogspot.com.br/2008_06_01_archive.html
6) https://en.wikipedia.org/wiki/Molecular_lesion
8 ) https://en.wikipedia.org/wiki/DNA_glycosylase
9) http://www.csun.edu/~cmalone/pdf360/Ch15-2repairtanspose.pdf
10) http://www.nature.com/nature/journal/v434/n7033/full/nature03458.html
11) http://www.nature.com/nature/journal/v434/n7033/full/nature03458.html
12) http://creationsafaris.com/crev200503.htm
13) http://fire.biol.wwu.edu/trent/trent/DNAsearchrescue.pdf
14) http://www.genome.jp/kegg-bin/show_pathway?ko03410
15) https://en.wikipedia.org/wiki/DNA_damage_(naturally_occurring)
16) http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer
17) http://creation.com/dna-best-information-storage
18) http://nrc58.nas.edu/RAPLab10/Opportunity/Opportunity.aspx?LabCode=50&ROPCD=506451&RONum=B7083
19) http://www.ladydavis.ca/en/DNAdamage?mid=ctl00_MainMenu_ctl00_TheMenu-menuItem002-subMenu-menuItem001
20) http://truemedmd.com/wp-content/uploads/2015/01/Shapiro.1997.BostonReview1997.ThirdWay.pdf



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New Way That Cells Fix Damage To DNA Discovered

Repair through alkyltransferase-like proteins (ATLs)

DNA damage repair is a fascinating topic in cell biology. Fascinating because the cell's repair mechanisms are so incredible. What's more the mechanisms are coordinated in a sophisticated control network. As one researcher put it, "it’s almost as if cells have something akin to a computer program that becomes activated by DNA damage, and that program enables the cells to respond very quickly."

Now a new mechanism has been discovered which repairs DNA alkylation damage (the erroneous addition of carbon groups to DNA bases). The new mechanism links two previously known mechanisms. Here is how one science writer describes these two mechanisms:

The DNA repair process that removes such toxic "lesions" is known as base repair, and uses a protein called AGT (O6-alkylguanine DNA-alkytransferase) to remove the alkyl group before DNA replicates. The protein essentially sticks a chemical finger inside the DNA to flip the damaged [base] out from the DNA helix structure so that its adduct is exposed and can be transferred from the [base] to a part of its protein structure. The [base] is now repaired and can rejoin cytosine with three hydrogen bonds linking them.

AGT is believed to act alone, but there is another, unrelated repair process—nucleotide excision repair (NER)—that uses lots of proteins in its pathway. This repair occurs when bulky adducts stuck to bases distort the sleek shape of the DNA helix. Then a whole group of proteins come in and remove a patch of bases that includes the adduct, and DNA polymerase follows and fills in the patch while adding the correct base back.

The new mechanism uses alkyltransferase-like proteins (ATLs) which are similar to the AGT protein. Like AGT, ATL attacks the DNA base that has suffered alkylation damage. But the ATL protein distorts the DNA structure significantly, and thus triggers the nucleotide excision repair (NER) mechanism.

This sophisticated and coordinated repair sequence was found in all three domains of life (prokaryotes, eukaryotes and archaea). For evolutionists this forces the absurd conclusion that such a sophisticated DNA repair interaction evolved early on. Before there was so much as an amoeba, evolution had worked wonders. The earliest crude cells must not have been so crude after all. Evolution incredibly worked miracles in those heady days of early life. As the researchers write:

Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life.

This conclusion that complexity comes early is often forced on evolutionists, in spite of the evolutionary expectations to the contrary.



http://www.sciencedaily.com/releases/2009/06/090610133451.htm

A team of researchers at The Scripps Research Institute and other institutions has discovered a new way by which DNA repairs itself, a process that is critical to the protection of the genome, and integral to prevention of cancer development.

Scientists who study the repair of the DNA bases, which make up the information in the human genome, had known of only one type of method that cells use to fix a specific kind of damage to their DNA, but in the June 11, 2009 issue of Nature, the team found a novel way—one that combines elements from the known mechanisms and an unrelated second method that was previously not known to play a role in this type of DNA repair.

"We found a connection between the known DNA repair processes that people did not know was there," says Professor John Tainer, a member of the Skaggs Institute for Chemical Biology at Scripps Research, who led the study with Geoffrey P. Margison of the University of Manchester (United Kingdom) and Anthony E. Pegg of the Pennsylvania State University College of Medicine. "This changes the game, and gives us something important to look for in cancers that are resistant to chemotherapy."

This new mechanism is controlled by alkyltransferase-like proteins (ATLs), whose structure and function had been unknown and which had been identified only in bacteria and yeast. In addition to describing the function of ATLs, in the new study the scientists showed that ATLs exist in a multicellular organism, the sea anemone, which suggests this protein or its cousins in terms of repair activity also exist in other species, including humans.

Known Strategies for DNA Repair

Damage occurs to a cell's DNA on a continuing basis from outside sources, such as radiation and UV light, and from activities that go on day by day inside the cell. Most of this damage consists of damage to the DNA bases adenine, cytosine, guanine, and thymine. These bases pair up together inside the DNA double helix—adenine and thymine join together, and guanine and cytosine link to each other and their sequence forms the information in the human genome.

These bases can be chemically modified in a number of ways, including by alkylation, in which an alkyl group (or "adduct") is transferred onto a guanine base. When this happens, one of the hydrogen bonds holding guanine and cytosine together is removed, increasing the chances that thymine will be inserted across from guanine during DNA replication. If DNA is replicated with this "transition" error, a mutated gene results, so the information is changed. This can lead to harmful results, like cell death or cancer.

As shown in the reported work, this kind of damage occurs, for example, when chemicals derived from cigarette smoke stick to guanine, or when chemotherapy agents put an alkyl adduct onto guanine.

But that is where DNA repair mechanisms come in, which is good in the case of chemicals from cigarettes, but not so desirable when they repair genetic damage purposely induced by chemotherapy drugs intended to kill cancer cells.

The DNA repair process that removes such toxic "lesions" is known as base repair, and uses a protein called AGT (O6-alkylguanine DNA-alkytransferase) to remove the alkyl group before DNA replicates. The protein essentially sticks a chemical finger inside the DNA to flip the damaged guanine out from the DNA helix structure so that its adduct is exposed and can be transferred from the guanine to a part of its protein structure. The guanine is now repaired and can rejoin cytosine with three hydrogen bonds linking them.

AGT is believed to act alone, but there is another, unrelated repair process—nucleotide excision repair (NER)—that uses lots of proteins in its pathway. This repair occurs when bulky adducts stuck to bases distort the sleek shape of the DNA helix. Then a whole group of proteins come in and remove a patch of bases that includes the adduct, and DNA polymerase follows and fills in the patch while adding the correct base back.

A New Way

Before the new study, ATLs were believed to be involved in DNA damage responses, because they protected cells from DNA alkylation damage in lab experiments, but no one understood how they worked or what they did. In the new study, the team describes ATLs' role.

The scientists undertook a series of structural, genetic, and biochemistry experiments on the protein and determined its structure, both alone and with a guanine that had a methyl adduct and another with a smoking-derived adduct stuck on it. They found that the ATL structure looks like AGT. It, too, had a chemical finger that can rotate a damaged guanine base out from the DNA helix, but it doesn't remove the adduct like AGT does. Instead, ATL binds tightly to the damaged guanine and bends the DNA in a way that is more pronounced than what AGT does for repair.

"Base flipping by ATL is like a switch that activates the NER pathway, which then removes the alkyl adduct from the guanine," says first author Julie Tubbs, a research associate at Scripps Research. "So we believe that ATL is conceptually acting like a bridge, connecting the two DNA repair pathways—base and NER—together. This is a surprisingly general mechanism to channel specific base damage into the general NER pathway."

Before the new study, scientists also didn't know if ATLs functioned outside of single celled organisms. In the new study, however, the scientists discovered ATLs in two types of ancient organisms, archaeal bacteria and in sea anemone, suggesting this new bridging pathway may be general to most cells and organisms.

"What's especially important about these newly discovered ATLs is that we now know that ATLs exist in all domains of life, so it is very likely that ATL was common to the evolutionary branches before complex eukaryotes [single-celled or multicellular organisms whose cells contain a distinct membrane-bound nucleus]," Tainer says. "This suggests higher eukaryotes, including mammals and humans, will either have an ATL or have lost or replaced it with a protein of analogous function."

If ATLs are found in humans, Tainer sees that either inhibiting or bolstering their function could aid cancer therapy. Inhibiting DNA repair would help chemotherapy effectively destroy cancer cells. Augmenting ATL function could help protect sensitive tissue, such as bone marrow, that is easily destroyed during cancer treatment.

"There are all kinds of exciting ideas to emerge from this research," says Tainer. "For one thing, we now know what to look for when we see resistance to some chemotherapies."

In addition to Tainer, Margison, Pegg, and Tubbs, authors of the new study are Vitaly Latypov, Amna Butt, Andrew Marriott, Amanda J. Watson, Barbara Verbeek, Gail McGown, and Mary Thorncroft of the University of Manchester; Sreenivas Kanugula of the Pennsylvania State University College of Medicine; Manana Melikishvili and Michael G. Fried of the University of Kentucky; Rolf Kraehenbuehl and Oliver Fleck of Bangor University; Mauro F. Santibanez-Koref of the University of Newcastle-upon-Tyne; Christopher Millington and David M. Williams of the University of Sheffield; Lisa A. Peterson of the University of Minnesota; and Andrew S. Arvai and Matthew D. Kroeger of Scripps Research. Tainer also holds a position at Lawrence Berkeley National Laboratory.

The study was supported by the National Institutes of Health, The Skaggs Institute for Chemical Biology, U.S. Department of Energy, the North West Cancer Research Fund, Cancer Research-UK, and CHEMORES.




New Powerful DNA Repair Single Protein Complex Discovered 1

Normal but dangerous strand breaks occur with the DNA double helix about 10 times a day in every cell due to ultraviolet light and radiation damage, etc. This creates an emergency. If these breaks are not quickly repaired, serious chromosomal rearrangements can occur that lead to cancer. The first responder to rush to the rescue looks like an octopus, and wraps around the accident scene to perform the repairs. These mechanical technicians in the cell are now beginning to be understood after 10 years of research.

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Energy. A press release at the Scripps Research Institute states:

“In a paper published in an Advance Online Edition of Nature Structural and Molecular Biology March 27, 2011, the scientists say that the complex’s motor molecule, known as Rad50, is a surprisingly flexible protein that can change shape and even rotate depending on the task at hand.”

The research paper stated that the components of this super protein structure are “conserved,” which means unevolved. The report continues:

“The finding solves the long-standing mystery of how a single protein complex known as MRN (Mre11-Rad50-Nbs1) can repair DNA in a number of different, and tricky, ways that seem impossible for “standard issue” proteins to do, say team leaders Scripps Research Professor John Tainer, Ph.D., and Scripps Research Professor Paul Russell, Ph.D., who also collaborated with members of the Lawrence Berkeley National Laboratory on the study.”

The report further reads:

“The scientists say that the parts of the complex, when imagined together as a whole unit, resemble an octopus: the head consists of the repair machinery (the Rad50 motor and the Mre11 protein, which is an enzyme that can break bonds between nucleic acids) and the octopus arms are made up of Nbs1 which can grab the molecules needed to help the machinery mend the strands.”

When rescue workers initially arrive at an emergency scene, the first thing they must do is identify and assess the injuries. The report explains the general idea of the process:

“When MRN senses a break, it activates an alarm telling the cell to shut down division until repairs are made. Then, it binds to ATP (an energy source) and repairs DNA in three different ways, depending on whether two ends of strands need to be joined together or if DNA sequences need to be replicated.”

Tainer explains: “The same complex has to decide the extent of damage and be able to do multiple things. The mystery was how it can do it all.”

In this study, Tainer and Russell were able to produce crystal and X-ray scattering images of parts of where Rad50 and Mre11 touched each other. The four (4) images of what these proteins look like when the complex is bound to ATP and when it is not are displayed above.

The four images demonstrate how ATP binding allows Rad50 to drastically change its shape. When not bound to ATP, Rad50 is flexible and floppy, but bound to ATP, Rad50 snaps into a ring that presumably closes around DNA as if it were an octopus in order to repair it.

The research also reveals a busy transport system that Trainer refers to as “big movement on a molecular scale” involved with the repair operation. He added, “Rad50 is like a rope that can pull. It appears to be a dynamic system of communicating with other molecules.”

Aside from the complex cellular machinery involved in this process, the functions being performed are also quite sophisticated. This set of proteins has the ability to sense damage, then be transported substantial distances to the accident site to initiate repairs. The damage must be assessed, a choice must be made as to the correct procedure to restore the damage, and the proper materials must be retrieved to perform the repair work.

1) https://dennisdjones.wordpress.com/2011/03/28/new-powerful-dna-repair-single-protein-complex-discovered/



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Special DNA polymerases are used in emergencies to repair DNA

If a cell's DNA is heavily damaged, the repair mechanisms are often insufficient to cope with it. In these cases, a different strategy is called into play, one that entails some risk to the cell. The highly accurate replicative DNA polymerases stall when they encounter damaged DNA, and in emergencies cells employ versatile but less accurate back-up polymerases to replicate through the DNA damage. Human cells contain more than l0 such DNA polymerases, some of which can recognize a specific type of DNA damage and specifically add the nucleotide required to restore the initial sequence. Others make only "good guesses," especially when the template base has been extensively damaged. These enzimes are not as accurate as the normal replicative polymerases when they copy a normal DNA sequence. For one thing, the backup polymerases lack exonucleolytic proofreading activity; in addition, many are much less discriminating than the replicative polymerase in choosing which nucleotide to initially incorporate. Presumably, for this reason, each such polymerase molecule is given a chance to add only one or a few nucleotides. Aithough the details of these fascinating reactions are still being worked out, they provide elegant testimony to the care with which organisms maintain the integrity of their DNA.

Its remarkable how the author chooses words which indicate design. Isnt it rather the creator who gave special care in order to provide integrity of the DNA ?

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Mismatch Repair (MMR) 1

DNA mismatch repair is a highly conserved pathway in which our cells repair base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Mismatch repair systems maintain the integrity of our genomes by suppressing non-homologous recombination and was recently shown to play a role in DNA damage signalling in eukaryotic cells. Defects in MMR increase the spontaneous mutation rate, and have been associated both hereditary and sporadic cancers.

The proteins unique to MMR were first identified in prokaryotes, in which the loss of such proteins resulted in increased mutations and a mutated phenotype. These proteins are known as the “Mut” proteins. Of all the “Mut” proteins, MutS, MutL, MutH are essential in detecting the mismatch and directing repair machinery to it.

Brief View of MMR Steps

The first step in the MMR system involves efficient recognition of helical distortions (mismatches) resulting from nucleotide misincorporation or DNA polymerase slippage. After that, the newly synthesized DNA strand containing the incorrect information must be selectively removed and re-synthesized. Strand discrimination is an essential feature of all MMR systems; in its absence, a replication error is just as likely to be used as a template for repair as it is to be repaired. Whereas the latter steps in MMR require proteins involved in general DNA metabolic processes, the initial mismatch recognition and removal steps require specialized Mut proteins, which are highly conserved evolutionarily.

1) http://warforscience.blogspot.com.br/2010/01/answering-creationist-claims-part-6-dna.html

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Molecular Machines Are Amazing Alone, but When They Cooperate -- Wow! 1

Our genomes are protected by multiple levels of monitoring and repair, so that most of us carry on from day to day, completely oblivious of the multiple information-guided processes in our cells that make life work. There are systems that can fix double-stranded breaks. There are systems that can replace incorrect DNA bases (letters) in the code. There are even machines that can push the panic button when errors are catastrophic, causing a damaged cell to shut down.

For science to comprehend these systems, it needs a framework fit for the information age. It needs familiarity with robotics and multi-level control. The biology of Charles Darwin's antiquated Victorian world, which imagined systems emerging from unguided processes, is hopelessly inadequate. Darwin did not foresee, and could not have fathomed, the technology at the basis of life.

A simple way to envision the action of UvrD in prokaryotes to promote RNA polymerase backtracking is the train engine analogy, in which a locomotive (RNA polymerase) encounters a railroad track buckle (DNA damage) and stalls. A second locomotive (UvrD in blue) is positioned at the rear end of the first locomotive, and the UvrD throttle is engaged to quickly and efficiently drag the stalled RNA polymerase locomotive away from the track buckle, so the repair crew can fix it. In this scenario, UvrD utilizes its force-producing ATP hydrolysis to haul the large 5-subunit RNA polymerase complex of ~400 kiloDalton backward, overcoming the driving force of the elongating RNA polymerase to translocate again toward the damage and obstruct the buckle. Once the lesion is repaired, RNA synthesis can resume.  2





2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049952/figure/F1/
1) http://www.evolutionnews.org/2014/01/molecular_machi_3081111.html

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As to; ‘DNA codes are far more sophisticated than their human counterparts, and they also have a variety of repair mechanisms.’

Repair mechanisms in DNA include:

A proofreading system that catches almost all errors
A mismatch repair system to back up the proofreading system
Photoreactivation (light repair)
Removal of methyl or ethyl groups by O6 – methylguanine methyltransferase
Base excision repair
Nucleotide excision repair
Double-strand DNA break repair
Recombination repair
Error-prone bypass


http://www.newgeology.us/presentation32.html

further note;

Quantum Dots Spotlight DNA-Repair Proteins in Motion – March 2010
Excerpt: “How this system works is an important unanswered question in this field,” he said. “It has to be able to identify very small mistakes in a 3-dimensional morass of gene strands. It’s akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour.” Dr. Bennett Van Houten – of note: A bacterium has about 40 team members on its pothole crew. That allows its entire genome to be scanned for errors in 20 minutes, the typical doubling time.,, These smart machines can apparently also interact with other damage control teams if they cannot fix the problem on the spot.
http://www.sciencedaily.com/releases/2010/03/100311123522.htm

Moreover, “Quantum Information/Computation” which is not reducible to the materialistic framework of neo-Darwinism (A. Aspect), is found to be integral to DNA;

Quantum Information/Entanglement In DNA & Protein Folding – short video
http://www.metacafe.com/watch/5936605/

In the preceding video, ‘Gretchen’ asked if quantum entanglement/information could also somehow be measured in protein structures, besides just DNA, and it turns out that quantum entanglement/information has already been detected in protein structures. Here is one such measure;

Proteins with cruise control provide new perspective:
Excerpt: “A mathematical analysis of the experiments showed that the proteins themselves acted to correct any imbalance imposed on them through artificial mutations and restored the chain to working order.”
http://www.princeton.edu/main/news/archive/S22/60/95O56/

further notes;

3-D Structure Of Human Genome: Fractal Globule Architecture Packs Two Meters Of DNA Into Each Cell – Oct. 2009
Excerpt: the information density in the nucleus is trillions of times higher than on a computer chip — while avoiding the knots and tangles that might interfere with the cell’s ability to read its own genome. Moreover, the DNA can easily unfold and refold during gene activation, gene repression, and cell replication.
http://www.sciencedaily.com/releases/2009/10/091008142957.htm

DNA Optimized for Photostability
Excerpt: These nucleobases maximally absorb UV-radiation at the same wavelengths that are most effectively shielded by ozone. Moreover, the chemical structures of the nucleobases of DNA allow the UV-radiation to be efficiently radiated away after it has been absorbed, restricting the opportunity for damage.
http://www.reasons.org/dna-soaks-suns-rays

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living creatures must have elaborate DNA repair machinery. University of Chicago biologist James Shapiro points out that:

all cells from bacteria to man possess a truly astonishing array of repair systems which serve to remove accidental and stochastic sources of mutation. Multiple levels of proofreading mechanisms recognize and remove errors that inevitably occur during DNA replication. … cells protect themselves against precisely the kinds of accidental genetic change that, according to conventional theory, are the sources of evolutionary variability. By virtue of their proofreading and repair systems, living cells are not passive victims of the random forces of chemistry and physics. They devote large resources to suppressing random genetic variation and have the capacity to set the level of background localized mutability by adjusting the activity of their repair systems

Shapiro, J.A., A Third Way, Boston Review, p. 2, February/March 1997

http://creation.com/DNA-repair-enzyme#txtRef5

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8 DNA errors are scanned electrically on Mon Jun 15, 2015 4:51 pm

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DNA errors are scanned electrically

Location of DNA damage by charge exchanging repair enzymes: effects of cooperativity on location time

How DNA repair enzymes find the relatively rare sites of damage is not known in great detail. Recent experiments and molecular data suggest that individual repair enzymes do not work independently of each other, but interact with each other through charges exchanged along the DNA. A damaged site in the DNA hinders this exchange. The hypothesis is that the charge exchange quickly liberates the repair enzymes from error-free stretches of DNA. In this way, the sites of damage are located more quickly 2


New Scientists : Enzymes scan DNA using electric pulse

ENZYMES that repair DNA may check for mutations by sending electrons along sections of the strand, in much the same way that electricians test for faults in circuits. The mechanism might explain how enzymes locate problems in the genome fast enough to correct them.

Most genetic mutations are caused by free radicals scavenging electrons from DNA. This "oxidative damage" introduces errors such as base-pair mismatches when the strand replicates. If these errors build up they can be extremely harmful.

All organisms have enzymes that can repair the errors. They bind to DNA and are thought to move slowly along the strand, testing each base pair to see if there is a mismatch. But Jacqueline Barton of the California Institute of Technology in Pasadena is not convinced this is what happens. "That would take a lot of time," she says - too long to allow the genome to be comprehensively scanned. ... 3

DNA-mediated charge transport for DNA repair

The [4Fe4S] cluster of these base excision repair enzymes,
containing a unique ligating peptide sequence, is thus well
designed for its function
: robust in solution as [4Fe4S]2, stable
to oxidizing and reducing conditions of the cell, but, once buried
within DNA, activated to carry out redox chemistry.
A Role for DNA CT in DNA Repair. Importantly, our electrochemical
data indicate that DNA-mediated CT involving the [4Fe4S]
cluster of MutY is feasible. The primary lesson learned from our
many studies of DNA CT chemistry is that DNA CT is exquisitely
sensitive to perturbations in base pair structure . Indeed
we have shown DNA CT electrochemistry as a diagnostic tool for
mutations and lesions in DNA. Might DNA repair
proteins, MutY in particular, similarly exploit DNA CT to detect
mismatches and lesions in DNA?
Based on results of others, within the cell, MutY contains
a [4Fe4S]2 cluster . On binding DNA nonspecifically,
as our results indicate, MutY undergoes a shift in redox potential,
and the 32 couple becomes accessible, so that the
cluster may become oxidized and release an electron in a
DNA-mediated reaction. Upon oxidation, MutY could then
serve, through DNA-mediated CT, to reduce an alternate DNA
repair protein, perhaps another MutY, bound at a distant site
a along the duplex. The electrochemistry data indicate that such a
DNA-mediated process is possible. Moreover, association of two
MutY equivalents on the DNA template has been proposed
based on kinetic experiments . In the reduced form, the
DNA affinity of MutY should be diminished, facilitating dissociation
of the protein from its DNA site. We propose that this
process, as described, constitutes a scan of this region of the
genome. Significantly, the region must be well stacked and
contain no mismatches or lesions for CT to occur. Also shown
is association of MutY to a region containing a mismatch, where
the associated stacking perturbation would not permit DNAmediated
CT to occur. Here, the protein would remain associated
with the DNA, processively diffusing to the mismatch site
on a slower time scale. Data in support of this slower processive
mechanism for MutY (80) as well as descriptive models (81, 82)
have also been reported. The CT scanning mechanism does not
obviate these schemes. Instead, the DNA CT scanning strategy
confines the search to a manageable regime within the genome.
Furthermore, although the specificity ratio, 10–1,000, of these
repair proteins for their target site versus well-matched DNA is
too low to explain preferential recognition of mismatches within
the genome, this small level of specificity is sufficient for target
binding within the subset of mismatch-containing strands. 4


Electric DNA

Our cells have elaborate machinery to repair DNA. But with 3 billion ‘letters’ worth of information in every cell, there is a lot to scan for errors.

However, unbroken DNA conducts electricity, while an error blocks the current. Now Dr Barton has found that some repair enzymes exploit this. One pair of enzymes lock onto different parts of a DNA strand. One of them sends an electron down the strand. If the DNA is unbroken, the electron reaches the other enzyme, and causes it to detach. I.e. this process scans the region of DNA between them, and if it’s clean, there is no need for repairs.

But if there is a break, the electron doesn’t reach the second enzyme. This enzyme then moves along the strand until it reaches the error, and fixes it. This mechanism of repair seems to be present in all living things, from bacteria to man 1

This is another striking example of ingenious design inside the cell which points to a intelligent creator that made all living things.

1) http://creation.com/electric-dna#endRef5
2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142343/
3) http://www.newscientist.com/article/mg18024171.200-enzymes-scan-dna-using-electric-pulse.html
4) http://authors.library.caltech.edu/627/1/BOOpnas03.pdf

http://reasonandscience.heavenforum.org/t2043-dna-repair#3498

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DNA could not survive without repair mechanisms.

http://www.icr.org/article/few-reasons-evolutionary-origin-life-impossible/

DNA, as is true of messenger-RNA, transfer-RNA, and ribosomal-RNA, is destroyed by a variety of agents, including ultraviolet light, reactive oxygen species, alkylting agents, and water. A recent article reported that there are 130 known human DNA repair genes and that more will be found. The authors stated that "Genome |DNA| instability caused by the great variety of DNA-damaging agents would be an overwhelming problem for cells and organisms if it were not for DNA repair emphasis mine)."6 Note that even water is one of the agents that damages DNA! If DNA somehow evolved on the earth it would be dissolved in water. Thus water and many chemical agents dissolved in it, along with ultraviolet light would destroy DNA much faster than it could be produced by the wildest imaginary process. If it were not for DNA repair genes, the article effectively states, DNA could not survive even in the protective environment of a cell! How then could DNA survive when subjected to brutal attack by all the chemical and other DNA-damaging agents that would exist on the hypothetical primitive Earth of the evolutionists?

What are the cellular agents that are necessary for DNA repair and survival? DNA genes! Thus, DNA is necessary for the survival of DNA! But it would have been impossible for DNA repair genes to evolve before ordinary DNA evolved and it would have been impossible for ordinary DNA to evolve before DNA repair genes had evolved. Here we see another impossible barrier for evolution. Furthermore, it is ridiculous to imagine that DNA repair genes could have evolved even if a cell existed. DNA genes encode the sequences of the hundreds of amino acids that constitute the proteins that are the actual agents that are involved in DNA repair. The code in the DNA is translated into a messenger RNA (mRNA). The mRNA must then move to and be incorporated into a ribosome (which is made up of three different ribosomal RNAs and 55 different protein molecules). Each amino acid must be coupled to a transfer RNA specific for that amino acid, and the coupling requires a protein enzyme specific for that amino acid and transfer-RNA. Responding to the code on the messenger RNA and utilizing the codes on transfer RNA's, the appropriate amino acids, attached to the transfer RNAs, are attached to the growing protein chain in the order prescribed by the code of the messenger RNA. Many enzymes are required along with appropriate energy. This is only a brief introduction to the incredible complexity of life that is found even in a bacterium.



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Why Error detection/correction Mechanisms Require Intelligence 1

The one thing I find myself repeatedly having to explain to Darwinists is that the very existence error detection/correction mechanisms within the genome not only pre-supposes intelligence but absolutely, totally requires pre-knowledge of correct system state.
For some reason, probably related to their other mental illnesses, the Darwinians never get this. They seem incapable of logical response to existing facts. Most of the people I know, including some of the very well known scientists that often attempt debate with Darwinists know this to be a salient fact. As soon as one puts forth simple, clear and logical evidence that their theory doesn’t add up it’s like their minds go into infinite loops and no further reasoning is possible. Their minds are put on HOLD.
Therefore, in the case of error detection/correction mechanisms in the genome here’s a little analogous test I thought up to help Darwinists figure out why the very existence of such mechanisms pre-suppose intelligence.
Test:


Write a coherent sentence in English on a piece of paper.  Make it say around 20-30 words long. In the sentence you create make sure to include a good number of glaring grammatical and spelling errors.
Now, find a monolingual Chinese or (other such language not using the English alphabet) person and ask them to find and correct the mistakes.

Obviously they are not going to either find or correct anything at all, for the whole is gibberish to them.
Do you see? No pre-knowledge of English grammar, symbolism, spelling etc. necessarily equals no ability to either detect or correct error.
Do you see how the same principle applies to any such error trapping/correcting in any syntactic system – including biological ones like DNA/RNA?
Good.
Design is the inevitable and ONLY scientifically correct explanation. Period.
This is not hard.

Information in DNA also has transmission and error checking protocols used as well as the translation mechanisms of RNA. These, by default, cannot be acquired in mere matter. They must be designed.Error can never be detected without an obligatorily preceeding knowledge or convention on what is correct.

1) https://borne.wordpress.com/category/darwinismintelligent-design/page/3/

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New class of DNA repair enzyme discovered 1

When the structure of DNA was first discovered, scientists imagined it to be extremely chemically stable, which allowed it to act as a blueprint for passing the basic traits of parents along to their offspring. Although this view has remained prevalent among the public, biologists have since learned that the double helix is in fact a highly reactive molecule that is constantly being damaged and that cells must make unceasing repair efforts to protect the genetic information that it contains.
"It's a double-edged sword," said Brandt Eichman, associate professor of biological sciences and biochemistry at Vanderbilt University, who headed the research team that made the new discovery. "If DNA were too reactive then it wouldn't be capable of storing genetic information. But, if it were too stable, then it wouldn't allow organisms to evolve."
The DNA double-helix has a spiral staircase structure with the outer edges made from sugar and phosphate molecules joined by stair steps composed of pairs of four nucleotide bases (adenine, cytosine, guanine and thymine) that serve as the basic letters in the genetic code.
There are two basic sources of DNA damage or lesions: environmental sources including ultraviolet light, toxic chemicals and ionizing radiation and internal sources, including a number of the cell's own metabolites (the chemicals it produces during normal metabolism), reactive oxygen species and even water.
"More than 10,000 DNA damage events occur each day in every cell in the human body that must be repaired for DNA to function properly," said first author Elwood Mullins, a postdoctoral research associate in the Eichman lab.
The newly discovered DNA repair enzyme is a DNA glycosylase, a family of enzymes discovered by Tomas Lindahl, who received this year's Nobel prize for recognizing that these enzymes removed damaged DNA bases through a process called base-excision repair. It was the first of about 10 different DNA repair pathways that biologists have identified to date.
In base-excision repair, a specific glycosylase molecule binds to DNA at the location of a lesion and bends the double-helix in a way that causes the damaged base to flip from the inside of the helix to the outside. The enzyme fits around the flipped out base and holds it in a position that exposes its link to the DNA's sugar backbone, allowing the enzyme to detach it. After the damaged base has been removed, additional DNA-repair proteins move in to replace it with a pristine base.
Eichman and his collaborators discovered that a glycosylase called AlkD found inBacillus cereus -- a soil-dwelling bacterium responsible for a type of food poisoning called the "fried rice syndrome" -- works in a totally different fashion. It does not require base flipping to recognize damaged DNA or repair it.
Seven years ago, Eichman's group discovered that AlkD had a structure unlike any of the other glycosylases. The researchers determined that the enzyme was able to locate damaged DNA that has a positive electrical charge. This is the signature of alkylation, attaching chains of carbon and hydrogen atoms of varying lengths (methyl, ethyl etc.), to specific positions on the damaged base. Positively charged alkylated bases are among the most abundant and detrimental forms of DNA damage. However, they are highly unstable, which has made them very difficult to study.
Now the researchers have captured crystallographic snapshots of AlkD in the act of excising alkylation damage and have shown that the enzyme doesn't use base flipping. Instead, they have determined that AlkD forms a series of interactions with the DNA backbone at and around the lesion while the lesion is still stacked in the double helix. Several of these interactions are contributed by three amino acids in the enzyme that catalyze excision of the damaged base.
According to the researchers, the AlkD mechanism has some remarkable properties:

  • It can recognize damaged bases indirectly. AlkD identifies lesions by interacting with the DNA backbone without contacting the damaged base itself.


  • It can repair many different types of lesions as long as they are positively charged. By contrast, the base-flipping mechanism used by other glycosylases relies on a relatively tight binding pocket in the enzyme, so each glycosylase is designed to work with a limited number of lesions. AlkD doesn't have the same type of pocket so it isn't restricted in the same way. Instead, the catalytic mechanism that AlkD uses is limited to removing positively charged lesions.


  • It can excise much bulkier lesions than other glycosylases. Base excision repair is generally limited to relatively small lesions. A different pathway, called nucleotide excision repair, handles larger lesions like those caused by UV radiation damage. However, Eichman's team discovered that AlkD could excise extremely bulky lesions, such as the one caused by the antibiotic yatakemycin, which is beyond the capability of other glycosylases.



"Our discovery shows that we still have a lot to learn about DNA repair, and that there may be alternative repair pathways yet to be discovered. It certainly shows us that a much broader range of DNA damage can be removed in ways that we didn't think were possible," said Eichman. "Bacteria are using this to their advantage to protect themselves against the antibacterial agents they produce. Humans may even have DNA-repair enzymes that operate in a similar fashion to remove complex types of DNA damage. This could have clinical relevance because these enzymes, if they exist, could be reducing the effectiveness of drugs designed to kill cancer cells by shutting down their ability to replicate."

1) http://www.sciencedaily.com/releases/2015/10/151029190840.htm

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Error checking - evidence of design

https://iaincarstairs.wordpress.com/about/

To make matters worse, the materialists, championed by outspoken critics of religion such as Richard Dawkins, put all biological development down to random mutations and declare the universe a blind and aimless place in which consciousness is a meaningless byproduct.  But the cellular processes within the human body reproduce perfectly hundreds of trillions of times from the starting point as a single cell, and manufacture and error check trillions of complicated proteins and assembly devices over the course of a lifetime.

So, what we witness every day, what passes without comment in all living beings (which should be subject to the same physical tendencies as all such processes in the past) shows no sign of random wanderings at all, in fact, quite the reverse: the error checking procedures are so sophisticated that a tiny manufacturing error of a single wrongly placed amino acid can be detected in a device such as connectin which has 26,9216 precisely placed amino acid components, the entire assembly sent back, stamped for disassembly, and the parts recycled.  How such an elaborate error detection system, filled with safeguards and protective devices, a system needed to maintain all biological life can itself arise from mistakes, faults, errors and other disasters – a single one of which can bring an intact human being to its knees in agony – seems impossible to imagine.

http://en.wikipedia.org/wiki/DNA_repair

Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the genome (but cells remain superficially functional when so-called "non-essential" genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister chromatid as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as translesion synthesis as a last resort.

http://creation.com/how-life-works

The only reason that DNA functions as well as it does is that cells come equipped with an amazing array of cooperative DNA repair mechanisms. For example, polymerase replication during cell division might produce 6 million errors per cell, but then proofreading machinery can reduce this to 10,000 and then mis-match repair machinery could reduce this to 100.

http://www.nature.com/scitable/topicpage/dna-damage-repair-mechanisms-for-maintaining-dna-344

Because DNA is the repository of genetic information in each living cell, its integrity and stability are essential to life. DNA, however, is not inert; rather, it is a chemical entity subject to assault from the environment, and any resulting damage, if not repaired, will lead to mutation and possibly disease. Perhaps the best-known example of the link between environmental-induced DNA damage and disease is that of skin cancer, which can be caused by excessive exposure to UV radiation in the form of sunlight (and, to a lesser degree, tanning beds). Another example is the damage caused by tobacco smoke, which can lead to mutations in lung cells and subsequent cancer of the lung. Beyond environmental agents, DNA is also subject to oxidative damage from byproducts of metabolism, such as free radicals. In fact, it has been estimated that an individual cell can suffer up to one million DNA changes per day (Lodish et al., 2005).

During the cell cycle, checkpoint mechanisms ensure that a cell's DNA is intact before permitting DNA replication and cell division to occur. Failures in these checkpoints can lead to an accumulation of damage, which in turn leads to mutations.

CPDs and 6-4 PPs are both repaired through a process known as nucleotide excision repair (NER). In eukaryotes, this complex process relies on the products of approximately 30 genes.

http://en.wikipedia.org/wiki/Nucleotide_excision_repair

Nucleotide excision repair is a DNA repair mechanism. [2] DNA damage occurs constantly because of chemicals (ie intercalating agents), radiation and other mutagens.




Additional DNA Repair mechanisms


NER and photoreactivation are not the only methods of DNA repair. For instance, base excision repair (BER) is the predominant mechanism that handles the spontaneous DNA damage caused by free radicals and other reactive species generated by metabolism

Thus, enzymes known as DNA glycosylases remove damaged bases by literally cutting them out of the DNA strand through cleavage of the covalent bonds between the bases and the sugar-phosphate backbone. The resulting gap is then filled by a specialized repair polymerase and sealed by ligase. Many such enzymes are found in cells, and each is specific to certain types of base alterations.

DNA glycosylases


http://en.wikipedia.org/wiki/DNA_glycosylase

DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond.

there is ‘base excision repair’: special enzymes called DNA glycosylases run down the DNA molecule, detect the damaged ‘letter’, grab it, put it in a specially shaped pocket, then chop it out. Then other enzymes repair the resulting gap.



Yet another form of DNA damage is double-strand breaks, which are caused by ionizing radiation, including gamma rays and X-rays. These breaks are highly deleterious. In addition to interfering with transcription or replication, they can lead to chromosomal rearrangements, in which pieces of one chromosome become attached to another chromosome. Genes are disrupted in this process, leading to hybrid proteins or inappropriate activation of genes. A number of cancers are associated with such rearrangements. Double-strand breaks are repaired through one of two mechanisms: nonhomologous end joining (NHEJ) or homologous recombination repair (HRR). In NHEJ, an enzyme called DNA ligase IV uses overhanging pieces of DNA adjacent to the break to join and fill in the ends. Additional errors can be introduced during this process, which is the case if a cell has not completely replicated its DNA in preparation for division. In contrast, during HRR, the homologous chromosome itself is used as a template for repair.

http://en.wikipedia.org/wiki/Non-homologous_end_joining

http://www.ncbi.nlm.nih.gov/pubmed/18166982

Mutations in an organism's DNA are a part of life. Our genetic code is exposed to a variety of insults that threaten its integrity. But, a rigorous system of checks and balances is in place through the DNA repair machinery. 


http://creation.com/DNA-repair-enzyme

Shapiro, J.A., A Third Way, Boston Review, p. 2, February/March 1997

all cells from bacteria to man possess a truly astonishing array of repair systems which serve to remove accidental and stochastic sources of mutation. Multiple levels of proofreading mechanisms recognize and remove errors that inevitably occur during DNA replication. … cells protect themselves against precisely the kinds of accidental genetic change that, according to conventional theory, are the sources of evolutionary variability. By virtue of their proofreading and repair systems, living cells are not passive victims of the random forces of chemistry and physics. They devote large resources to suppressing random genetic variation and have the capacity to set the level of background localized mutability by adjusting the activity of their repair systems.


http://www.creationscience.com/onlinebook/LifeSciences39.html

DNA cannot function without hundreds of preexisting proteins,but proteins are produced only at the direction of DNA. Because each needs the other, a satisfactory explanation for the origin of one must also explain the origin of the other. Therefore, the components of these manufacturing systems must have come into existence simultaneously.  This implies creation.

In each human, tens of thousands of genes are damaged daily!e Also, when a cell divides, its DNA at times is copied with errors. Every organism has machinery that identifies and repairs damaged and mistranslated DNA. Without such repair systems, the organism would quickly deteriorate and die. If evolution had happened, each organism would have become extinct before these DNA repair mechanisms could evolve.

Life’s complexity is mind boggling—not something that random processes could ever produce.


http://www.evolutionnews.org/2014/01/molecular_machi_3081111.html

Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

it stops and waits. The problem is, when it stops, it stalls over the break, preventing repair machines from reaching it. Not to worry. Everything is under control.

   In the new study, the NYU School of Medicine researchers reveal how another enzyme called UvrD helicase acts like a train engine to pull the RNA polymerase backwards and expose the broken DNA so a repair crew can get to work....

   The study by Dr. Nudler's group and colleagues in Russia used a battery of biochemical and genetic experiments to directly link UvrD to RNA polymerase and to demonstrate that UvrD's pulling activity is essential for DNA repair. The lab results also suggest that UvrD relies on a second factor, called NusA, to help it pull RNA polymerase backwards. Those two partners then recruit a repair crew of other proteins to patch up the exposed DNA tracks before the train-like polymerase continues on its way.

Each of these machines is powered by ATP and built by the same DNA that it repairs! One can't help but recall Dean Kenyon's reaction in Unlocking the Mystery of Life to this kind of discovery: "This is absolutely mind-boggling to perceive, at this scale of size, such a finely-tuned apparatus, a device that bears the mark of intelligent design and manufacture." Each of these machines is complex enough in itself. To see them working as a cooperative team is all the more wonderful.

More on how a mystery was solved by the researchers at NYU:

   According to Dr. Nudler, his team's study offers a convincing justification for a puzzling phenomenon known as pervasive transcription, which he calls "one of the most enigmatic and debated subjects of molecular biology." The question, he says, boils down to this: Why do RNA polymerases transcribe most of the genome within humans and other organisms, converting vast stretches of DNA to RNA, when only a tiny fraction of those resulting RNA transcripts will ever prove useful? Isn't that RNA polymerase activity a waste of energy and resources?

   "Our results imply that a major role of RNA polymerase is to patrol the genome for DNA damage," he says. "This is the only molecular machine that is capable of continuously scanning the chromosomes for virtually any deviation from the canonical four bases in the template strand: A, T, G and C." The polymerase's extensive transcription activity, then, might be well worth the effort if its continuous vigilance also ensures that any DNA damage gets fixed through the assistance of the pulling factors and other collaborators.

So it wasn't wasteful after all. And we know from the ENCODE project that most (if not all) of the non-protein-coding DNA is important for regulation and other functions. This amplifies the importance of RNA polymerase's constant "vigilance" in inspecting the entire genome.

Included in the article are descriptions of bad consequences when RNA polymerase, UvrD helicase and the other machines don't work properly (perhaps due to mutations in their genes). Hair can turn brittle; children may age prematurely; others may suffer from exposure to sunlight. Those are the lucky ones who don't die without this vital repair mechanism.

The study reveals a "major new role of RNA polymerase and other enzymes in DNA repair." Notably, it's not the only repair system. Our genomes are protected by multiple levels of monitoring and repair, so that most of us carry on from day to day, completely oblivious of the multiple information-guided processes in our cells that make life work. There are systems that can fix double-stranded breaks. There are systems that can replace incorrect DNA bases (letters) in the code. There are even machines that can push the panic button when errors are catastrophic, causing a damaged cell to shut down.

For science to comprehend these systems, it needs a framework fit for the information age. It needs familiarity with robotics and multi-level control. The biology of Charles Darwin's antiquated Victorian world, which imagined systems emerging from unguided processes, is hopelessly inadequate. Darwin did not foresee, and could not have fathomed, the technology at the basis of life.

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13 DNA Search and Rescue Machine Imaged in Action on Sat Jan 30, 2016 3:13 am

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DNA Search and Rescue Machine Imaged in Action

DNA is amazing enough, but its automatic error-correction utilities are enough to stagger the imagination.  There are dozens of repair mechanisms to shield our genetic code from damage; one of them was portrayed in Nature1 March 31 (see also analysis by Sheila David in the same issue2) in terms that should inspire awe.
    Imagine a huge encyclopedia written on beads, in strands many miles long.  The words of the book are inscribed in letter beads along the strand.  Now imagine that, tied to the primary strand, is a twin strand with beads representing the “negatives” of the primary beads, such that when the strands are separated, exact copies can be made.  Every once in awhile, the strands are separated by a machine.  Floating beads are attracted to the negative beads, lining up to form exact copies of the book or portions thereof.  This is a simplified view of DNA transcription and replication.  What happens, however, if the wrong bead, or a defective bead, becomes attached to the negative?  For books, that could misspell a word or produce gibberish, but in living organisms, the consequences could be disastrous.
    Now picture little machines that regularly traverse the string of beads.  Because the shapes of the beads differ according to the letters on them, this machine is able to find typos.  Let’s say that a letter “C” is always supposed to pair with a letter “G” on the strand.  The proofreading machine feels every bead, and if it finds that particular mismatch, it ejects the incorrect bead so that another correct one can be fastened on by another machine.  This is a simplified view of “base-excision repair” (BER) that actually takes place in your body, all the time.


    The strands in a cell are, of course, DNA, and the beads are called nucleotides, or bases.  Of the four bases in DNA (C, G, A, and T) cytosine or C is always supposed to pair with guanine, G, and adenine, A, is always supposed to pair with thymine, T.  The enzyme studied by Banerjee et al. in Nature is one of a host of molecular machines called BER glycosylases; this one is called human oxoG glycosylase repair enzyme (hOGG1), and it is specialized for finding a particular type of error: an oxidized G base (guanine).  Oxidation damage can be caused by exposure to ionizing radiation (like sunburn) or free radicals roaming around in the cell nucleus.  The normal G becomes oxoG, making it very slightly out of shape.  There might be one in a million of these on a DNA strand.  While it seems like a minor typo, it can actually cause the translation machinery to insert the wrong amino acid into a protein, with disastrous results, such as colorectal cancer.  This little machine has an important job.3  How does it work?
    The machine latches onto the DNA double helix and works its way down the strand, feeling every base on the way.  As it proceeds, it kinks the DNA strand into a sharp angle.  It is built to ignore the T and A bases, but whenever it feels a C, it knows there is supposed to be a G attached.  The machine has precision contact points for C and G.  When the C engages, the base paired to it is flipped up out of the helix into a slot inside the enzyme that is finely crafted to mate with a pure, clean G.  If all is well, it flips the G back into the DNA helix and moves on.  If the base is an oxoG, however, that base gets flipped into another slot further inside, where powerful forces yank the errant base out of the strand so that other machines can insert the correct one.


    Now this is all wonderful stuff so far, but as with many things in living cells, the true wonder is in the details.  The thermodynamic energy differences between G and oxoG are extremely slight – oxoG contains only one extra atom of oxygen – and yet this machine is able to discriminate between them to high levels of accuracy.  David says, “DNA-repair enzymes amaze us with their ability to search through vast tracts of DNA to find subtle anomalies in the structure.  The human repair enzyme 8-oxoguanine glycosylase (hOGG1) is particularly impressive in this regard because it efficiently removes 8-oxoguanine (oxoG), a damaged guanine (G) base containing an extra oxygen atom, and ignores undamaged bases” (emphasis added in all quotes).  The team led by Anirban Banerjee of Harvard, using a clever new stop-action method of imaging, caught this little enzyme in the act of binding to a bad guanine, helping scientists visualize how the machinery works.
    Some other amazing details are mentioned about this molecular proofreader.  It checks every C-G pair, but slips right past the A-T pairs.  The enzyme, “much like a train that stops only at certain locations,” pauses at each C and, better than any railcar conductor inspecting each ticket, flips up the G to validate it.  Unless it conforms to the slot perfectly – even though G and oxoG differ in their match by only one hydrogen bond – it is ejected like a freeloader in a Pullman car and tossed out into the desert.  David elaborates:



Calculations of differences in free energy indicate that both favourable and unfavourable interactions lead to preferential binding of oxoG over G in the oxoG-recognition pocket, and of G over oxoG in the alternative site.  This structure [the image resolved by the scientific team] captures an intermediate that forms in the process of finding oxoG, and illustrates that the damaged base must pass through a series of ‘gates’, or checkpoints, within the enzyme; only oxoG satisfies the requirements for admission to the damage-specific pocket, where it will be clipped from the DNA.  Other bases (C, A and T) may be rejected outright without extrusion from the helix because hOGG1 scrutinizes both bases in each pair, and only bases opposite a C will be examined more closely.


How many linemen does it take to repair your strands?  The researchers explain, “Only 50,000 molecules of hOGG1 protect the entire 6 x 109 base-pair nuclear genome of a diploid human cell, hence the enzyme must have developed an efficient mechanism for distinguishing oxoG from the four nucleobases in normal DNA.”  50,000 repairmen for 6 billion bases: that’s one repairman for every 120,000 letters, comparable to a skilled proofreader checking every letter of a 20,000 word document for one specific kind of typo.  Then there are all the other proofreaders that look for other kinds of mistakes.4




1Banerjee et al., “Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA,” Nature 434, 612 - 618 (31 March 2005); doi:10.1038/nature03458.
2Sheila S. David, “Structural biology: DNA search and rescue,” Nature 434, 569 - 570 (31 March 2005); doi:10.1038/434569a.
3See “Life without DNA Repair,” in PNAS, 1997.  It lists 13 BER enzymes including this one.  Studies on mice are described: “mutants show various combinations of defective embryogenesis, tissue-specific dysfunction, hypersensitivity to DNA-damaging agents, premature senescence, genetic instability, and elevated cancer rates.”
4The authors mention another paralogous enzyme, 3-methyladenine DNA glycosylase (AlkA), which is not as “fastidious” as hOGG1, because it “does occasionally excise adenine residues from undamaged DNA.”  But there may be reasons for the differences in fidelity; some may have to work under stressful conditions, and repair as much as they can within constraints of time or other factors.  JBC Online says that AlkA has “a remarkably versatile active site.”  This reminds us that intelligent design does not mean perfection of every detail, but “constrained optimization”: achieving the combination of features that produces a “sweet spot” with best overall performance.  The proof of the pudding for DNA repair is in the performance itself: no one watching a race horse, cormorant (05/24/2004) or champion triathlete in action could argue with the assertion that the suite of repair enzymes in living things appears optimized to achieve an extremely high degree of fidelity under a wide range of conditions and stress factors.


OK, Darwin Party: checkmate.  Natural selection cannot act without accurate replication, yet the protein machinery for the level of accuracy required is itself built by the very genetic code it is designed to protect.  Explain that!  If the Darwinists cannot provide a plausible mechanism whereby nonliving chemicals, by chance, hit upon a means of replicating information-bearing molecules accurately, there would have been no evolution, because any gains would have been drowned in the errors of subsequent generations.
    It would have been challenging enough to explain accurate translation alone in a primordial soup, but now throw in some free radicals and radiation, and any information gained would have quickly been destroyed through accumulation of errors.  So accurate replication and proofreading are required for the origin of life.  How on earth could proofreading enzymes emerge, especially with this degree of fidelity, when they depend on the very information that they are designed to protect?  Think about it.  This is a catch-22 for Darwinists.  No wonder none of the authors of these two articles dared whisper the word evolution.  The gig is up; we might as well not even waste any time arguing about Hobbit man (03/25/2005), peppered mice (04/18/2003) and what IMAX films to show (03/23/2005).  Proofreading codes by chance?  And a complex suite of translation machinery without a designer?  Anyone with a head screwed on is not going to want such nonsense taught in public schools (03/24/2005).
    If we can just sweep away the cobwebs of musty Darwinian thinking out of our minds for a moment, we can begin to enjoy the wonder of these incredible mechanisms.  If the ancients could understand that creation demands a Creator by looking at the sun, or a bird, or a baby, how much more we today with all the revelations about cell biology and molecular machines?  The grand oratorio of creation is being unveiled, a little at a time, into a hallelujah chorus that deserves our most worshipful applause – indeed, a standing ovation. 


http://creationsafaris.com/crev200503.htm

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15 Cell Repairs its RNA, Too on Sat Jan 30, 2016 3:53 am

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Cell Repairs its RNA, Too   

The cell has elaborate ways to safeguard its genetic library by repairing DNA, but now scientists are finding the same enzymes can also repair RNA.  In the Feb. 20 issue of Nature, Begley and Samson of MIT discuss the findings of Aas et al that RNA methylation damage can be repaired by the same AlkB enzyme that repairs DNA.  This is surprising because RNA and proteins were considered more expendable than DNA, but they explain why it makes sense (emphasis added):


Why, though, should it be necessary to repair damaged RNA?  The answer could be that although DNA is the final arbiter of genetic information, RNA is essential for the most basic biological processes.  RNA-based primer sequences are required for DNA replication; and mRNAs, transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) are all needed during the elaborate process of protein synthesis.  Even the formation of peptide bonds by ribosomes (the cell’s protein-making machines) turns out to require catalysis mediated by rRNAs.  Moreover, a battery of small, non-protein-coding RNAs regulates a variety of other cellular processes.
    So maintaining RNA integrity is important for proper cellular function.  And repairing damaged RNA may be more efficient than destroying it and starting again.  Ribosome assembly is a complex, energy-intensive process, and it is not hard to imagine that the thrifty repair of damaged rRNA would be preferable to disassembling or discarding an entire ribosomal particle.


Another surprise is that the repair mechanism seems to be able to distinguish between DNA and RNA, and between toxic methylation damage and normal biological methyl groups attached to some RNAs.  Begley and Samson think it not unlikely that DNA and RNA might overlap in other ways, such as in cell signalling.
Update  06/16/2003:  In the June 17 issue of Current Biology, Alfonso Bellacosa and Eric G. Moss from the Fox Chase Cancer Center in Philadelphia remind us that “RNA in a cell is subject to many of the same insults as DNA“ and that “the ‘information content’ of cellular RNA is greater than that of the chromosomal DNA” because almost all of RNA’s sequences have functional significance (messenger RNA and transfer RNA), whereas only 3% of the DNA has coding potential.  Since RNA shows significant response to anticancer agents, the authors suppose that newly-discovered RNA repair pathways are important for preventing cancer:

A cell has a great investment in its RNAs – they are working copies of its genomic information.  The study of mRNA biogenesis in the last few years has revealed an elaborate surveillance mechanism involving factors such as the UPF proteins that culls aberrantly spliced mRNAs and mRNAs with premature termination codons.  There might be a hint that such RNA quality control mechanisms go awry in cancers, just as DNA quality control mechanisms do, where aberrantly spliced transcripts accumulate in a tumor.  Now that the gates are open, we may have a flood of studies on the RNome [the RNA genome] stability and cancer.

This aggravates the chicken-and-egg problem for proponents of natural mechanisms.  In the “RNA World” hypothesis for the origin of life, RNA performed both the information storage and enzymatic functions before these roles were outsourced to DNA and proteins.  But how could RNA repair itself?  If RNA needs to be protected from damage, the protein repair system would have needed to be there from the beginning.  Proponents of natural mechanisms might surmise that different primitive RNAs worked side by side to repair each other, but that strains credibility for a hypothesis already far-fetched.
    In typical evolutionary lingo, Begley and Samson blow smoke about what nature produced (emphasis added): “It seems that, for each human protein, parameters have evolved to distinguish between RNA and DNA,” they speculate, and in another place, “It might be that the RNA-demethylation activity of AlkB-like proteins evolved to regulate biological RNA methylation, and that the repair of aberrant, chemical methylation is fortuitous.”  Ask them how the cell evolved these things, and you’ll probably get a quizzical look, as if “Why are you asking such a dumb question?  I don’t know.  It just had to.  We’re here, aren’t we?”


http://creationsafaris.com/crev0203.htm




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16 Electric DNA and Mind on Sat Feb 06, 2016 2:32 pm

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Electric DNA and Mind

The many electrical factors related to brain function bolsters the theory that mind might consist of electromagnetic fields, gradients and currents (one of several theories). Posts have described how in the developing fetus electrical synapses lay out the detailed brain structure with chemical synapses built on this template. Other posts have shown how brain regions used synchronous waves for communication at the same time neuron’s action potential communicates through a wired current.


Now, recent research shows that DNA functions as an electrical wire in a complex circuit. Critical enzymes that repair DNA have an electrical mechanism involving clusters of iron and sulfur. These metallic clusters allow proteins that are part of the genetic and epigenetic complexes to move electrons. These same clusters operate in many other biological processes including photosynthesis and mitochondrial energy production. Since this research is just beginning, other electric mechanisms could be involved in the complex function of DNA. Do these electrical properties allow DNA networks to respond instantly to mind? How important are these newly discovered electrical properties of DNA and are they related to a theory that electromagnetic forces connect mind, matter and brain? What is the relation of electric DNA and mind?

Many Forms of Brain Electricity



Several previous posts describe the many ways that electricity is involved in brain function. Just as matter and energy can’t be separated, there is no way to separate electrical and chemical synapses. They are critical for each other’s function. Flow of electricity through widespread electrical synapses produces the intricate wiring diagram of the fetal brain. This same process is used to repair neurons by first creating an electrical current and then re building the axon along it. A previous post described how electrical synapses are critical for the ordinary functioning of chemical synapses and vice versa. Many other electric events occur at the level of the protein ion channels sitting in the cell’s membrane and the voltage gated receptors. The sum of all of these effects is called the electrical gradient that has its own effects.




Synchronous electrical brain waves are formed when a group of neurons oscillate with the same frequencies. Two brain regions use beta waves to communicate the color of a memory, while two different regions at the same time oscillate beta waves to communicate the spatial orientation.These regions are sharing information in the form of electrical brain waves, while the neuronal axons share electrical information in the form of wiring triggering chemical synapses. Previous posts describe many other ways that brain waves communicate (see Neuronal Networks & Brain Waves). Gamma waves trigger different brain regions to fire neurons and to oscillate. Background electricity can affect individual neurons to spike.


In any region of the brain the many different types of electricity form a gradient of voltage potential and an electrical field. Additive electrical flow occurs near parallel columns of neurons. The folded cortical gyri create different electrical fields. Inhibitory neurons have gradients related to the cell body and the dendrites. Some regions of he brain such as the hippocampus have more of the faster electrical synapses to help neuroplasticity. The many properties of these gradients have been described in previous posts. One important function of the gradient is forming morphogen information fields that determine the shape of bodily organs and limbs. (see post Electrical Fields Guiding 3D Shape of Cells and Organs). After neuronal injury, electrical synapses appear and hold neuronal structures together while repair occurs in the chemical wiring synapses.


The morphogen field includes all the ways that cells communicate including electricity, molecules in the intracellular space, nanotubes and secreted chemical signals. They form an information field of geometry that allow the three dimensional development of organs and limbs. Please seeprevious post for a discussion of how this affects the creation of cancer and organs. Cancers form their own new organs with their own community electrical phenomena.


Not only neuronal axon spikes and brain waves correlate with mental states. Now, it has been seen that inter cellular electrical gradients are correlated with mental states. Clearly different types of thought correlate with groups of neurons communicating with synchronous brain waves.


Is mind in nature a form of electromagnetic information source that interacts constantly with molecules, including DNA? Cells demonstrate specific behaviors, which are influenced by the electrical fields. Their behavior is produced by the stimulation of genetic networks. All of the levels are influenced by these electrical events—the networks of cells, the individual cellular behavior and signaling and the genetic and epigenetic mechanisms. For movement of cells, when electrical and chemical gradients are in competition, the electrical gradient wins. The genetic networks are very critical in electric signaling because cells use protein ion channels imbedded in the membranes. These proteins affect distant actions and are very involved in creating the overall gradients. These are all regulated by genetic networks. Now, it is found that DNA itself has fundamental electric signaling properties and that the basic mechanisms that regulate DNA are based on electricity.


DNA Damage and Electricity



DNA is assaulted all day by photons from the sun and chemicals in the cell’s environment, often causing damage. Copying DNA billions of times per day, also, produces errors. [url=http://jonlieffmd.com/blog/human-brain/ http://jonlieffmd.com/blog/the-many-ways-neurons-repair-their-own-dna]Previous posts have described some of the many ways that cells patrol for errors and fix them[/url]. There are a variety of different types of damage and there are many systems of multiple large proteins that are involved in cutting, editing and reworking DNA when these problems arise. Other complex systems are involved in editing RNA, such as in the critical alternative RNA splicing, whereby many proteins are created out of a piece of DNA that used to be called a single gene.


To fix DNA errors, first the cell must be able to identify them. The errors can be DNA that is altered, replaced, mismatched or missing. Like protein folding where the greatest super computers cannot determine how the fold should occur, no one knows how these errors can possibly be found given the number of molecules to check.


Special proteins are used to locate the damage among billions of nucleotide pairs. These proteins ride along the DNA looking for errors. Up until now there has been no way to understand how these molecules can find one missing link out of billions. This has to be done very rapidly. There is not enough time to examine each strand. The proteins just aren’t fast enough.


Now, unique electric properties have been found in DNA that appears to allow the rapid detection of errors. One newly discovered property of DNA is that molecule conducts electricity as a wire. Very recently, this property has been linked to the ability of the cell to find abnormal spots for repair.
DNA’s electrical properties allow protein to produce electrons that travel along the DNA wire.

How Does DNA Conduct Electricity



Up until now it has not been clear whether the complex structure of DNA will increase the transmission of electrons or inhibit them. Some think that the side chains of amino acids stop the electron transfer, making DNA an insulator of electricity. Others find the opposite.


The backbone of the DNA molecule consists of sugars with phosphate molecules. In the center of the spiral are the nucleotide bases. The nucleotides are complex molecules with aromatic rings that produce unusual electron clouds. An electric current can flow along these electron clouds.
The early research in this field shows that DNA can conduct a current when it is placed between metals. Later, it was shown that live DNA conducts electricity a very long distance—hundreds of nucleotide bases. Proteins on the other hand only produced tiny currents noted in the quantum effects of tunneling, which appear to be related to enzyme mechanisms.


What has been striking about this new DNA research is that the electric current in DNA occurs when all of nucleotides have no errors. In this situation, the arrays of aromatic electron clouds create the currents, which travel for very long distances. If there are mismatches of the nucleotides through errors, such as missing, mismatched, or altered nucleotides, the current is disrupted.


One of the complex enzymes that repairs DNA is endonuclease III, which uses base excision repair (BER) described in a previous post. It identifies the error and cuts out the damaged nucleotides and then calls for other enzymes to insert the correct ones. These large enzymes create complexes together for this work. This enzyme uses a complex of iron and sulfur atoms that are very involved in electron transfer processes. These metals can either take or give an electron known as reduction and oxidation in chemistry.

How Does the Enzyme Find the DNA Errors and Fix Them

There are a wide variety of proteins that have iron-sulfur complexes, linked in different ways. These metallo-proteins are involved in many energy reactions in the mitochondria and in general metabolism with NADH and nitrogen fixation. In the mitochondrial transport system both Complex I and Complex II have many of these clusters. The clusters are involved in synthesis of lipoic acid. Significantly, these electron transfer clusters are found in many of the most significant enzymes regulating genes.
Iron and sulfur in enzymes are, often, used to help folding or altering the shape of the molecule. But, in Endonulcease III, the metals are very close to the DNA wire.





Phosphodiester bond
From DMacks

Endonucleases are a type of enzyme that cuts the phosphor-diester bond—the backbone of DNA—in a strand of DNA or RNA. Type I cuts the DNA bond randomly. There are many other specific versions called “restriction enzymes” that cut only at very specific sequences. Type III has been studied the most for its relation to electric DNA and cuts very specifically.
When connected to DNA, Endonuclease III changes its shape allowing the iron and sulfur atoms to give up electrons increasing its charge. This shape alteration makes the enzyme increase its hold on the DNA. The released electron travels along the DNA wire until it meets another Endonuclease III molecule attached to the DNA. The secondEndonuclease III molecule takes up the electron from the DNA. Taking up this electron, the second enzyme loosens its grip on the DNA.
As the electron travels along the DNA wire, it is stopped if there is a damaged spot, thus identifying a problem. When the error is identified, both of the repair molecules stay attached to the DNA wire on either side of the error, identifying a trouble spot. In fact, Endonuclease III does more. It helps communicate with other proteins, such as MutY, that come and fix the mutation.
This mechanism of exchanging electrons has now been shown to be extremely important in many techniques for repairing DNA. It, also, occurs occurs with many other repair proteins.

Many Major Genetic Enzymes Have Iron-Sulfur Electric Clusters



Many of the major enzymes that work with DNA have the iron sulfur clusters.. One important enzyme is polymerase that copies the DNA, as well asprimase that helps the polymerase. Another is helicase that unwinds DNA from the histone spools. Although the research is just beginning in these enzymes, all of them appear to engage in similar electric mechanisms.


Polymerase: The major enzymes that have been first identified to have these electrical properties are polymerases. These enzymes synthesize chains of nucleic acids assembling DNA and RNA molecules. They copy DNA and RNA templates using base pairing. Polymerase is the general term for enzymes that make larger molecules. The polymerase molecule that takes amino acids and makes them into long strands of protein is not called “polymerase” but rather theribsome. The electric mechanisms of the ribosome need to be elucidated. 


Primase: The primase enzyme is involved in copying DNA. It creates an RNA primer (in some organisms a DNA primer), which is used temporarily and then later removed by exonucleases. The RNA primer strand is then used to make copies of the single strand of DNA. This is a critical process because there is no known way that DNA is copied without the primer of either an RNA or DNA strand. (The DNA plus the primer is called DNA elongation). These enzymes work together. First an RNA strand made by primase then polymerase elongates it. Then a complex is created with two primase units, called the polymerase primase complex. Another primosome complex in bacteria includes primase and ahelicase. A helicase stimulates a primase making a small RNA primer and thenpolymerase adds more nucleotides.







From Smallbot

Helicases: These critical enzymes un-package the spooled genes from the histones They move along the backbone of the DNA in one direction separating two strands that are interlocked. These can be two strands of DNA, of RNA, or a combination of one strand of each. The mechanism uses energy from ATP. There are many different helicases that are used to separate genetic strands.
All of these have electrical iron-sulfur clusters and appear to have electrical mechanisms.

DNA, Cells and Electricity

Another surprising finding related to electricity in DNA is that the seven genes required to create the iron-sulfur clusters, have been stable in cells and molecules for billions of years. Also, 600 million years ago, long before neurons developed, an organism that later became jellyfish and sea anemones developed the genes for electrical communication. This means that electrical properties of genes started long before axons, electrical synapses and brain waves. They are basic to the cell, like DNA.
Another finding is that several cancers occur when the MutY enzyme is mutated and don’t have the metal clusters. Without the clusters, they can’t transfer the charges, and therefore more cancer causing damage can occur.


Once considered simple, the way that DNA is utilized to make messenger RNA is now known to be extremely complex with many layers of epigenetic mechanisms. There are many different triggers that unspool the complex histone that protect the DNA. Once open, many different proteins and RNAs trigger the activity that defines what parts of the genes will be utilized. There is an immense coordination at many levels that occurs during the production of the messenger RNAs, alternative RNA editing and production of proteins at the ribosome. Are the electric properties of DNA part of these larger processes? Also, social responses of the organism trigger these same genetic mechanisms. Could these coordinated electrical properties at many different orders of magnitude be related to an electromagnetic mind?


Electrical DNA Properties, Melanin and Skin Cancer



Recently, another unrelated electrical DNA finding was discovered. It remains to be incorporated into a more general theory of electric DNA. This other electrical property of DNA was found in studies about ultraviolet light causing cancers mutations in DNA in skin cells.


A recent with melanin shows intriguing connections with electron transfer and its effect on metabolism and DNA. Ultraviolet light induces reactive oxygen and nitrogen species molecules, which excite electrons in melanin fragments. While in the dark hours later after sun exposure, the electrical energy is transferred to DNA and damages it causing cancerous mutations. What is unusual about this is that the skin damage from ultraviolet light that damages DNA and triggers cancer, occurs by this mechanism while in the dark.
Induced by ultraviolet light, an electron is excited in melanin fragments and this electron is transferred to DNA. The transfer of this electron to DNA in the dark causes the same mutations as the ultraviolet light. This occurs by a special quantum state transferring energy of a photon from ultraviolet light to an electron in DNA.

Electric DNA and Mind

One theory of mind in nature is electromagnetic fields and gradients interacting with molecules, cells, organs and creatures. Mental events clearly are correlated with different brain waves, electrical communication along axon wires, electrical brain synapses and properties of electrical gradients. The details are elaborated in previous posts.
 

Recent research shows dramatic electrical effects of DNA and the complex enzymes that regulate DNA’s behavior. Many of these enzymes have clusters of iron-sulfur molecules that are critical in many of life’s electron energy transfers. DNA itself is noted to serve as a conducting wire of electricity when in between two metalloprotein molecules. But, it is certainly possible that there are other unknown electric properties of DNA with its very complex regulating machinery. All of the genetic editing (such as alternative RNA splicing) and cellular genetic engineering (such as making antibodies) could be conducted through electrical mechanisms. 


The very unusual effects of mind triggering specific genetic networks have, also, been elaborated in previous posts. Now, more of the very specific complexes that control DNA appear to have electric properties. DNA electrical mechanisms could be a way that an electromagnetic mind relates directly to the functions of the cell.



http://jonlieffmd.com/blog/human-brain/electric-dna-mind

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New instruction manual discovered for repairing broken DNA

https://www.sciencedaily.com/releases/2017/06/170608123648.htm

Drexel University and Georgia Institute of Technology researchers have discovered how the Rad52 protein is a crucial player in RNA-dependent DNA repair. The results of their study, published in Molecular Cell, reveal a surprising function of the homologous recombination protein Rad52. They also may help to identify new therapeutic targets for cancer treatment.

Radiation and chemotherapy can cause a DNA double-strand break, one of the most harmful types of DNA damage. The process of homologous recombination — which involves the exchange of genetic information between two DNA molecules — plays an important role in DNA repair, but certain gene mutations can destabilize a genome. For example, mutations in the tumor suppressor BRCA2, which is involved in DNA repair by homologous recombination, can cause the deadliest form of breast and ovarian cancer. Paper. (paywall) – Olga M. Mazina, Havva Keskin, Kritika Hanamshet, Francesca Storici, Alexander V. Mazin. Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Molecular Cell, 2017

the full paper:

http://www.sciencedirect.com.sci-hub.cc/science/article/pii/S1097276517303593

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