Thursday, May 24, 2007

An Important New Study Impacting Our Understanding of DNA Repair

Analysis Reveals Extent of DNA Repair Army is an article of the Howard Hughes Medical Institute which highlights the importance of genomic repair mechanisms; an important theme of this blog. The article, which notes a new study and its related publication in the journal Science, reveals some surprising findings noted by the study's senior author Stephen J. Elledge of Harvard. Quotes from the article in green:

"But precisely how cells monitor the integrity of their genomes, identify problems, and intervene to repair broken or miscoded DNA has been one of nature's closely held secrets. Now, however, a report in the journal Science describes a new database developed by a team of researchers from the Howard Hughes Medical Institute at Harvard Medical School that is providing the first detailed portrait of the army of more than 700 proteins that helps maintain DNA's integrity."

700 proteins involved in maintaining genomic integrity! The essential nature of the function is underlined by the sheer number of proteins involved. More from the article:

"The DNA damage response is a routine event in the life of any cell. Stress caused by environmental factors such as exposure to ultraviolet light, ionizing radiation or other environmental phenomena can cause DNA to break apart or rearrange its nucleotide base pairs in unhealthy ways. If such mutations are left unchecked, they can accumulate over time and lead, ultimately, to cancer or diabetes."

Note the consequences of unrepaired damage to DNA. It is actually more severe than indicated here. Damaged genomes produce defective proteins and impaired regulatory functions.

"Elledge explained that two critical enzymes, known in scientific shorthand as ATM and ATR, act like sensors to detect trouble and initiate the DNA damage response by engaging the cell's molecular repair apparatus."

Before an effective response to a problem can be mounted there must be a recognition that the problem exists. The essential nature of individual proteins is indicated by their functions.

"The results of this study illustrate the extraordinarily broad landscape of the DNA damage response, which extends far beyond what was anticipated from previous studies," he said."

Another indication of the importance of DNA repair. It clearly impacts medicine and should do the same with respect to theories about the origin and diversification of life.

"The proteins, known as Abraxas and RAP80, bind to the BRCA1 protein and form a complex that governs three essential modes of DNA damage control: damage resistance, genetic checkpoints that constrain cell proliferation, and DNA repair. There are three variants of this BRCA1 complex and one is mediated by Abraxas and RAP80, providing potentially different windows into the protective nature of the gene.

“We have to stop thinking about BRCA1 as a single entity. There are three complexes and which complex is doing what? That's what needs to get figured out,” Elledge said.

He noted that simply knowing that BRCA1 comes in three distinct flavors gives researchers the chance to sort out the role of each in the DNA damage response and the onset of tumors."


A pattern that is well entrenched in the history of research. Increasing knowledge is associated with the discovery of ever increasing biological complexity. Three varieties of BRCA1 correspond to three types of damage control: damage resistance, constraining cell proliferation by means of genetic checkpoints and DNA repair. This appears to be a sub-system in which all parts are needed to maintain effective genomic repair.

These are exciting research findings which alter our conception of just how vast and intricate is the network of proteins involved in containing DNA damage, as Elledge so aptly pointed out.

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8 Comments:

At 7:52 AM, Blogger dobson said...

It's interesting research isn't it? But unfortunately not any kind of evidence at all for any kind of intelligent design - care to differ?

 
At 9:51 AM, Blogger William Bradford said...

It is a basic theme of this blog that the increasing complexity and diversification of life evident in the fossil record would not have been possible without a functional genomic error detection and repair mechanism front loaded at the outset of life. Causes of genomic decay were present when the first life forms appeared. Uncorrected lesions accumulate and compromise affected organisms. That's an empirical claim. Impaired DNA repair functions have been identified as a major source of disease and cancer. Nature itself provides evidence of the essentialty of the associated mechanisms.

 
At 10:05 AM, Blogger dobson said...

Well, evolution predicts that any feature that provides a survival advantage will be conserved. In this case the researchers have found a number of genes which code for proteins that seem to be able to repair some kinds of DNA damage.

It's not stated anywhere how this is evidence for "front loading", a concept which has not been clearly defined (even on ID sites). And furthermore, nowhere in the article does it state that the authors found any evidence for intelligent design;

From what I can tell the authors of this paper are arguing that this elaborate defence system is an evolutionary adaptation designed to cope with ionising radiation.

It seems like just one of many evolutionary adaptations which server to help life-forms live to reproductive maturity; As I said, it's very interesting but not evidence of "front loading" or design.

 
At 11:25 AM, Blogger William Bradford said...

Once a genome is in place, replete with error repair mechanisms, variation is possible. The mutations we witness are actually breakdowns in the repair process which succeeds in correcting 99+ per cent of errors that actually occur. These repair mechanisms are intricate and multi-component and are specialized with respect to the type of damage they repair. Minimal repair systems could not evolve without a significant amount of mutations and time. But that's exactly the problem. The genomes of initial life forms would have been defenseless against natural degadative forces until they were in place. That's a recipe for extinction.

 
At 1:11 PM, Blogger dobson said...

And just how do you know that "Minimal repair systems could not evolve without a significant amount of mutations and time" or what precisely these "Minimal" systems are? And how do you know that lacking this is a "recipe for extinction". That's clearly a personal opinion and not a fact borne out of a lifetime of study of cellular evolution.

It is a conjecture that might be testable, but to my knowledge nobody has tested what the minumum ammount of "repair system" is, so neither you nor I are in a position to know authoritativly what is minimal and just how long that might take to evolve.

It just occurres to me that this minimum might be very small indeed. It's perfectly reasonable to suppose that the simplest life might have had a much simpler system or perhaps no repair system at all without facing the extinction scenario you propose.

Such a life form would not automatically become extinct if it lived in an environment with very little ionizing radiation, such as underwater.

Of course, this defencless organism might float to the surface and be struck by some kind of highly energetic particle, completely destroying it - but the death of one individual would not be the death of an entire species.

By the way, the simplest known organism is a single-celled ocean dwelling lifer-form with fewer than 1400 genes. It would be quite astonishing if this living fossil had the full compliment of radiation defences that a long-lived vertibrate has. I'd be willing to bet that this organism has a very simple defence, and it's precursors had something even simpler.

By the way, it seems pretty clear from the summary of this paper that it's authors consider radiation defence as an evolutionary adaptation, so I will re-iterate that the experts in this sort of thing do not appear to support your conjecture. Your notion that dna-repair mechanism could not have evolved would seem to be utterly unsupported by the paper you have chosen to cite.

 
At 6:02 PM, Blogger William Bradford said...

By the way, the simplest known organism is a single-celled ocean dwelling lifer-form with fewer than 1400 genes. It would be quite astonishing if this living fossil had the full compliment of radiation defences that a long-lived vertibrate has. I'd be willing to bet that this organism has a very simple defence, and it's precursors had something even simpler.

Your assumption of simplicity is erroneous. A post will address that issue more fully. Incidentally, the organism with the most intricate DNA damage and repair system is not a vertabrate but rather a unicellular organism. It's capabilities are so robust that it has even been found within nuclear reaction cores.

By the way, it seems pretty clear from the summary of this paper that it's authors consider radiation defence as an evolutionary adaptation, so I will re-iterate that the experts in this sort of thing do not appear to support your conjecture. Your notion that dna-repair mechanism could not have evolved would seem to be utterly unsupported by the paper you have chosen to cite.

The authors probably would claim that all human features resulted from evolutionary adaptation. That is not my concern or even the issue I raised. My point was that the paper supplied vital new data. I also indicated in a previous comment that whether or not an organism could survive without DNA repair mechanisms is an open question. It should be resolved experimentally.

 
At 10:17 AM, Blogger dobson said...

I also indicated in a previous comment that whether or not an organism could survive without DNA repair mechanisms is an open question. It should be resolved experimentally.

Sure, and until somebody does that verification the answer is that you and I just do not know - such a position is not sufficient grounds to assume that we have vital new evidence for the radical theory of ID.

At best we can say that anti-radiation defences, just like any other feature of life seems to have been an evolutionary adaption. The strongest evidence of this would be that different organisms seem to have inherited pretty much the same genes - which implies it first evolved in a common ancestor.


Your assumption of simplicity is erroneous. A post will address that issue more fully. Incidentally, the organism with the most intricate DNA damage and repair system is not a vertabrate but rather a unicellular organism. It's capabilities are so robust that it has even been found within nuclear reaction cores.

Well I was refering to a very spesific organism: Pelagibacter (which does not live in harsh environments), and not the one you were refering to. Pelagibacter is a very simple organism indeed, so it was not so much an assumption as an example.

It's a common mis-conception that vertibrates are "more evolved" than invertibrates or unicellular life forms. It's entirely thinkable that because of a pressure from the environment (e.g. high temperatures), an organism evolves a number of mechanisms to cope with it that stress.

As I said in my first comment on this thread - you've not actually made a case for "front-loading". You have pointed to some research that the ID community should do if they want to prove their point, but I'm skeptical that ID folks will ever have the desire to engage in this kind of basic research ever.

:-)

 
At 11:17 AM, Blogger William Bradford said...

At best we can say that anti-radiation defences, just like any other feature of life seems to have been an evolutionary adaption. The strongest evidence of this would be that different organisms seem to have inherited pretty much the same genes - which implies it first evolved in a common ancestor.

Munson's post already addressed your limited view of the DNA damage problem which extends considerably beyond radiation damage. Genomic damage is a problem for the origin of life. As Munson's post also indicated damaging agents were present when life first began. The evolution distraction is not pertinent to the point I have made repeatedly and observed it being ignored just as often.

Well I was refering to a very spesific organism: Pelagibacter (which does not live in harsh environments), and not the one you were refering to. Pelagibacter is a very simple organism indeed, so it was not so much an assumption as an example.

Pelagibacter does have DNA maintenance capacities as well as the capacity for recombination. Multiple enzymes are involved in these functions.

As I said in my first comment on this thread - you've not actually made a case for "front-loading". You have pointed to some research that the ID community should do if they want to prove their point, but I'm skeptical that ID folks will ever have the desire to engage in this kind of basic research ever.

As I've also repeatedly mentioned experimental evidence needs to settle these issues- not dogmatic beliefs. I'm skeptical critics will ever give up a basic tenet used as a prop for materialism regardless of expermental results.

These exchanges are becoming repetitious. This thread is closed for further comments.

 

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