> Would it be possible to devise some sort of virus which could somehow 'checksum' a given cell's DNA, and trigger cell-death if it doesn't match?
The problem is
a) there's a LOT of DNA in a cell, and a lot of a cells, so checksumming would logistically be pretty much impossible. This is assuming there is some mechanism by which you can "scan" the DNA, which in itself has a whole host of steric/timing issues (different chromatin states, how do you deal with cell division? histone methylation and DNA accessibility, DNA binding proteins inhibiting interaction with certain regions at different times)
b) the more conceptual issue is that DNA in cells have natural variation anyway. My DNA is different to yours, but DNA in some of my cells is going to be subtly different to DNA in other parts of me.
Mere implementation details! I shall apply for my patent forthwith. (That is, I have no idea what most of those terms mean) :p
The necessary internal variation sounds like it'd be the fatal flaw here, unless there's some way to determine 'good' changes and 'bad' changes.
As you said above, there are already repair/watchdog proteins for specific sections, so maybe that could be the basis for additional checking in other high-risk areas (Telomerase?).
So telomerase is slightly different - chromosomes have teleomeres at the end of each chromosome. These are just like long bits of "this-is-the-end-of-the-chromosome" DNA, like when you have a role of receipts and towards the end they have a red line through them to show the end is nigh.
You can think of it as like a "count-down timers". Every time a cell divides, the DNA gets doubled, so one cell doubles its DNA, creating two cells with identical DNA. When this happens, each of the telomeres in the new cell get a little bit shorter by a constant amount, and with this happening in a recursive way at some point they reach a critical length (Hayflick limit). At this point the cell knows it's undergone a certain number of divisions (~40 I think) meaning it's an old cell, so statistically it's likely to have picked up a few mutations. These mutations could make the cell less effective, or even worse, lead to some kind of disease (i.e. cancer), so as a precaution the cell initiates apoptosis. It's pretty clever - there may not be anything wrong, but there's a significant chance there is, the cell isn't perfect at detecting problems, so to avoid the risk to the rest of the body it kills itself.
Telomerase rebuilds telomeres, so is crucial in cells where lots of division is going on rapidly (such as embryonic cells) so cells can divide many more times by adding on the bit of teleomere that's lost. The problem is in cancer cells, telomerase is very often mutated into an “always on” position as it gives cells a way of being immortal. In normal cells telomerase isn't usually active, although it may have some other roles in pseduo-related areas. I was lucky enough to see Elizabeth Blackburn (Nobel prize winner for telomerase's discovery) speak a few years ago on this topic – it's really fascinating.
Proteins involved in DNA checking/repair are ones like ATM, Chk1, Chk2 , BRCA1, BRCA2, Rad51. There are many more, and they tend to work cooperativly together, though I can't remember the others off hand.
For more information regarding this kind of thing I'd really recommend Weinberg & Hanahan's The Hallmarks of Cancer [1]. Although published 11 years ago it's pretty much a “classic”, and gives a good overview of DNA damage and telomerase, albeit from a cancer viewpoint as opposed to generally.
The problem is
a) there's a LOT of DNA in a cell, and a lot of a cells, so checksumming would logistically be pretty much impossible. This is assuming there is some mechanism by which you can "scan" the DNA, which in itself has a whole host of steric/timing issues (different chromatin states, how do you deal with cell division? histone methylation and DNA accessibility, DNA binding proteins inhibiting interaction with certain regions at different times)
b) the more conceptual issue is that DNA in cells have natural variation anyway. My DNA is different to yours, but DNA in some of my cells is going to be subtly different to DNA in other parts of me.