Tuesday, September 26, 2006

DNA Damage and a Kinase Signaling Pathway

'A new effector pathway links ATM kinase with the DNA damage response' was published in Nature Cell Biology 6, 968 - 976 (2004). The article is focused on a signaling pathway. Identified kinases phosphorylate proteins in response to DNA damage.

A new pathway was reported. In this pathway ATM kinase targets Strap (a transcriptional cofactor) in signaling the DNA damage response. Like a row of falling dominos the kinase phosphorylation of Strap leads to the formation of a complex of proteins. There is also a regulatory effect resulting from Strap's enhancement of p53 acetylation. Strap's function, when phosphorylated, is to augment the DNA damage response. A conclusion drawn was that accumulation of Strap in the nucleus was a critical damage response regulator.

In a comment on a previous post Doug asked:

"How many separate processes and enzymes are utilized to safe-guard against the degradation of genomic information?"


The cited pathway reveals the effects of specific kinase enzymes in a signaling pathway of a DNA damage response.

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4 Comments:

At 12:56 AM, Anonymous Mike Godfrey said...

Hi William,
Just a quick question..im not very current on molecular biology,but it seems to me that the more complex an organism is-the more proofreading and general safeguards against DNA damage there are.Would you say this is a fair discription of the situation ?
If this is the case then it would seem to place limits on the amount of evolutionary change available to more complex organisms as random mutations would be corrected.
In fact it would support the view held by some such as Dr John Davidson :“A past evolution is undeniable, a present evolution undemonstrable.”I also remmember reading Simon conway morris's recent book 'Lifes Solution' describing the optimisation of the genetic code.As I worte in my blog:
Stephen J. Freeland and Laurence D. Hurst used computer simulations to look at exactly how efficient the genetic code is in relation to what might otherwise have been?

Freeland and Lawrence had to place within there computer program all the nuances seen in nature such as the observed increase in relative frequency of mutations due to mistakes seen at the third position of the triplet mRNA during translation. Mistakes occur frequently at this position due to a weak-binding affinity between mRNA and tRNA dubbed a ‘wobble’ by DNA’s co discoverer Francis Crick.

Codon’s which code for the same amino acid due to redundancy of the should usually differ by there last letters (third base) so the common mistakes generated by weak binding at the third base in a codon generate a (wobble). So mistakes at the third position in a codon often give the same amino acid as was initially intended.Freeland and Lawrence randomised the genetic code leading to a massive number of alternate possible codes, one in a hundred million then compared the efficiency in terms of redundancy .They produced the bell curve with almost all there computer generate codes being in the bell –when comparing the efficiency of the bell curve codes with the code we have within us they found our natural code was far far more efficient .

Freeland and Lawrence tell it like this ‘…the natural genetic code shows evidence of optimisation, two orders of magnitude higher than has been suggested previously…..under our model, of 1 million random variant codes produced ,only 1 better …than the natural code –our genetic code is quite literally 1 in a million !’

Could it be that Macroevolution was a 1 time only event ?
Cheers,
Mike

 
At 8:15 AM, Blogger William Bradford said...

Just a quick question..im not very current on molecular biology,but it seems to me that the more complex an organism is-the more proofreading and general safeguards against DNA damage there are.Would you say this is a fair discription of the situation?

Yes. I intend to continue a series of posts on the topic of error correction and damage control mechanisms. A failsafe option not yet discussed is a phenomenon known as apoptosis or the programmed death of cells. If the damage to DNA is too extensive the cell can in effect commit suicide. You can see that this would make sense for multi-cellular organisms. I'll respond to other comments you made when I have more time but wanted to get this off now.

Incidentally, I was unaware of your blog but traveled there before posting this comment. I enjoyed this visit. It makes me wonder how many blogs of interest there are about which I am unaware.

 
At 7:46 PM, Blogger William Bradford said...

If this is the case then it would seem to place limits on the amount of evolutionary change available to more complex organisms as random mutations would be corrected.

Correction mechanisms do limit mutations. Supporters of standard theories contend there are nevertheless sufficient mutations for a selection process. Assessing this is difficult and entails some unknowable factors such as mutation rates for non-existent common ancestors.

In fact it would support the view held by some such as Dr John Davidson :“A past evolution is undeniable, a present evolution undemonstrable.”

I've suggested an experiment involving a rapidly reproducing unicellular organism whose genome is engineered so as to be missing genes encoding a target mechanism. Place the organism under selective pressure and observe it to see if the genes or a subset of them evolve. The objection is that geologic time periods cannot be encompassed in a lab experiment.

I also remmember reading Simon conway morris's recent book 'Lifes Solution' describing the optimisation of the genetic code. As I worte in my blog:

Stephen J. Freeland and Laurence D. Hurst used computer simulations to look at exactly how efficient the genetic code is in relation to what might otherwise have been?

Freeland and Lawrence had to place within there computer program all the nuances seen in nature such as the observed increase in relative frequency of mutations due to mistakes seen at the third position of the triplet mRNA during translation. Mistakes occur frequently at this position due to a weak-binding affinity between mRNA and tRNA dubbed a ‘wobble’ by DNA’s co discoverer Francis Crick.

Codon’s which code for the same amino acid due to redundancy of the should usually differ by there last letters (third base) so the common mistakes generated by weak binding at the third base in a codon generate a (wobble). So mistakes at the third position in a codon often give the same amino acid as was initially intended.Freeland and Lawrence randomised the genetic code leading to a massive number of alternate possible codes, one in a hundred million then compared the efficiency in terms of redundancy .They produced the bell curve with almost all there computer generate codes being in the bell –when comparing the efficiency of the bell curve codes with the code we have within us they found our natural code was far far more efficient .

Freeland and Lawrence tell it like this ‘…the natural genetic code shows evidence of optimisation, two orders of magnitude higher than has been suggested previously…..under our model, of 1 million random variant codes produced ,only 1 better …than the natural code –our genetic code is quite literally 1 in a million !’


I believe the existence of the genetic code is excellent evidence for ID.

Could it be that Macroevolution was a 1 time only event ?
Cheers,
Mike


There is no evidence of life elsewhere in the universe and narrow range values exists for universal constants consistent with favorable conditions for life. Add the huge obstacles barring a plausible theory for life's origins and you have a basis upon which to hypothesize that life is the end-product of intelligence.

 
At 11:58 PM, Anonymous Mike Godfrey said...

Hi William'
thanks for your reply,
It seems strange that all these mechanism are devoted to restricting the number and diversity of DNA damage, yet 'random' mutation plus natural selection work best I think when theres a wide range of mutations to select for -antibiotic resistance a case in point.
It also seems as if there really isn't anything random about mutations -as these as Mike Gene says can be seen as a form of homeostasis -where in some instances of stress the organism can purposely increase the number of mutations, in a bit for survival.
Interesting stuff,
cheers,
Mike

 

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