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Author Topic:   Will mutations become less freqent?
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 20 of 25 (335961)
07-28-2006 6:20 AM
Reply to: Message 19 by capeo
07-28-2006 12:44 AM


From the amount of double strand break suggested the non-template nucleotides (which are stated to occur very often) would be intergrated at an amazing rate, more than is tenable except maybe in the case of a cancer. What am I missing?
I think once again the position of the break is critical. I'm not going to try and put any exact numbers on it, since our understanding of which genetic elements are important to normal cellular functional and organismal development are changing all the time, but most of our DNA seems to serve at best a structural function and is far less likely to be perturbed by the insertion of a few non-template nucleotides, certainly less so than by having a persistent DSB. In a coding region or a crtical regulatory region then such insertions certainly could be detrimental, but as a numbers game the chances are much higher that the insertion will have little effect.
TTFN,
WK

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 Message 21 by RAZD, posted 07-28-2006 7:34 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 22 of 25 (335995)
07-28-2006 8:46 AM
Reply to: Message 21 by RAZD
07-28-2006 7:34 AM


Now it seems that DNA is rather randomly broken into smaller segments and reformed as\when necessary (when duplication is needed?), so the whole system may be much more dynamic than is commonly envisaged.
I don't think this is an accurate characterisation of what happens during a DSB, there is a lot more to the structure of a chromosome than merely DNA. DNA in a chromosome is wrapped around nucleosomes which are structures composed of several proteins known as histones, both the packing of the DNA to the nucleosome and further modifications of the organisation of nucleosomes themselves can produce tighter packing of DNA into what is known as heterochromatin. Therefore even if DNA undergoes a DSB the two 'fragments' are not floating dissociated from one another but still joined together by the larger superstructure of the chromosome.
When duplication is needed -- but may it also be necessary to {open up - access the 'internal' folded structure} the DNA for other functions? And then have some mechanism to recombine it?
Not only when duplication is needed. If the break or insertion is in the coding region of an important housekeeping gene then a cells function may be severely compromised. Indeed this sort of damage to a tumour supressor gene could well be an important step towards the development of cancer.
Dna must normally be opened up from its compacted heterochromatic state if a gene is to be transcribed prior to protein synthesis. There is a constant dynamic restructuring of chromatin as and when certain genes are no longer required. Much of the regulation of this is provided by modifications to the histone proteins, specifically methylation and acetylation of the histones.
As well as the histones to fully 'open' the structure for transcription there are a number of enzymes which actively manipulate the DNA such as Helicases which seperate out the strands and Topoisomerases which actually cut the DNA in order to reform it topologically. Some Topoisomerases actually produce double stranded breaks in order to untangle chromosomes.
TTFN,
WK

This message is a reply to:
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