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repair really needed!

posted Apr 23, 2015, 10:57 PM by Rachel Aronoff   [ updated Apr 26, 2015, 12:25 AM ]
The latest shock from the MOOC course, now in week 7, is that one of the main needs for DNA repair in cells is *not* so much due to any external damaging agent, but is due to ribonucleotide incorporation into replicating chromosomes!  Apparently in yeast, appr. 10000 rNMPs are inserted per cell replication cycle, and for humans this number increases by 100 fold, for 1000000 (one million) of these events, that need to be repaired. One consequence of having incorporated rNMPs, for instance, is that DNA polymerase 'stalls' whenever one is encountered during DNA replication.  (Other base analogs are also occasionally incorporated during replication, like for instance dUMP or 5-bromo-uracil - if the latter is not repaired in time, a new G will be misincorporated - in other words another fixed mutation is added to the genome.)  While water hydrolysis and reactive oxygen species were discussed as other endogenous damaging processes in the AGiR! Prezi already, this really is an eye-opening fact, one with potentially long-reaching implications.*  (I should probably also edit the Prezi to include it! Btw, even if this presentation still has only had less than 135 views, a second very nice <3 and comment sure made me happy, while writing this post!  Thx, FO! :)   
hmmm….     
It is clear that repair in the cell is central and really necessary!   
In one other bit of news, that I hope will also be relevant for AGiR!, I plan to attend a seminar about single cell RNA analyses today!  yes!  watch out for more in this regard!  :)
Take care!   

* and actually (!) there is already work out there, for instance from the O'Donnell group at the Rockefeller, that implicates these inserted rNMPs in mismatch repair, perhaps not simply as 'mistakes,' but as yet another mechanism (outside the directionality of loaded replication factors, like the sliding clamp) by which the cell can tell which is the newly synthesised DNA strand (and thus the one that should be repaired in case of ambiguities)  

This phenomenon of rNMP insertion could thus again be thought of as another way that RNA is taking care of DNA (!), by helping make sure that repair processes don't result in compounding mistakes, fixing more errors in the genome as mutations... 

What do you think?