Mitochondrial Mutation Results
manofsan
20 Jul 2005
Here's an article:
http://www.betterhum...65/Default.aspx
Apparently, lab rats which can't proofread mitochondrial DNA as well, will also suffer faster age-related decline.
So will a study be done with lab rats that have hyperexpression of the DNA proofreader gene? Hopefully, that would show rats with increased lifespan.
Forgive me if I've asked this before, but when you have a single-stranded mutation, how do you tell (how does a proofreader enzyme tell) which is the mutated strand and which is the genuine? I could understand if DNA was 3-stranded, and then the odd man out is obviously the mutant. But when you're 2-stranded, how do you tell which strand is right?
http://www.betterhum...65/Default.aspx
Apparently, lab rats which can't proofread mitochondrial DNA as well, will also suffer faster age-related decline.
So will a study be done with lab rats that have hyperexpression of the DNA proofreader gene? Hopefully, that would show rats with increased lifespan.
Forgive me if I've asked this before, but when you have a single-stranded mutation, how do you tell (how does a proofreader enzyme tell) which is the mutated strand and which is the genuine? I could understand if DNA was 3-stranded, and then the odd man out is obviously the mutant. But when you're 2-stranded, how do you tell which strand is right?
JonesGuy
20 Jul 2005
Regarding your question: my answer is for a eukaryotic cell - the type of DNA inside your cell nucleus. The mitoDNA actually has a different method.
When DNA is replicated "mature" DNA is split in half (down the middle) and new DNA is replicated on each strand.
This means that each DNA strand is made up of an "mature" half and a "young" half. The "mature" half is actually chemically different, because (I believe) parts of it have been methylated.
The proofreader, when it runs into a discrepancy, will default to whatever was on the "mature" strand, assuming that the mistake was made while replicating the new DNA onto the mature strand. Most of the errors in your DNA would be made during replication anyway, so it's a pretty good system.
There are other mechanisms when both DNA strands are mature (like in a non-dividing cell). And these mechanisms just operate under 'rules of thumb', and aren't all that accurate. The band-aids operate in such a fashion as to do the least damage.
When DNA is replicated "mature" DNA is split in half (down the middle) and new DNA is replicated on each strand.
This means that each DNA strand is made up of an "mature" half and a "young" half. The "mature" half is actually chemically different, because (I believe) parts of it have been methylated.
The proofreader, when it runs into a discrepancy, will default to whatever was on the "mature" strand, assuming that the mistake was made while replicating the new DNA onto the mature strand. Most of the errors in your DNA would be made during replication anyway, so it's a pretty good system.
There are other mechanisms when both DNA strands are mature (like in a non-dividing cell). And these mechanisms just operate under 'rules of thumb', and aren't all that accurate. The band-aids operate in such a fashion as to do the least damage.
ag24
20 Jul 2005
The answer for mitochondria is that the proofreading is done by the one half of the same enzyme whose other half does the DNA synthesis. Thus, the proofreader is automatically located to look specifically at the strand that's in the process of being synthesised.
apocalypse
26 Jul 2005
I was thinking that should we assume this effect holds in the longterm for nonmutants, this seems to create selective pressure in favor of cells who've more healthy mitochondrias, and it seems it may point to the limitations of s-cell tissue-renew-replenishment as being behind the degeneration and accumulation of cells with substantial defects.
Edited by apocalypse, 26 July 2005 - 12:23 PM.
Edited by apocalypse, 26 July 2005 - 12:23 PM.
