RUNNING THROUGH STOP SIGNS
March 28th, 2006
First author of this paper, Antonia Holway
These observations led us to imagine the possibility of a checkpoint conflict during early development. Conflict could arise if damaged chromosomes activated the checkpoint in an inappropriate manner, leading to disruption of the timing of cell division and developmental disaster. Thus the goal of the featured study was: do checkpoints ignore DNA damage during early development and, if so, how?
The results of this study have just been published in the Journal of Cell Biology. The answer is that worm embryos have evolved a pathway that actively silences the checkpoint when DNA damage is present. An interesting feature of this silencing pathway is that it uses a translesion polymerase to silence the checkpoint. Translesion DNA polymerases have the capacity to use damaged DNA as a template, but cells pay a price for this in the form of mutations, as translesion polymerases make mistakes at high frequency when copying DNA. The utilization of a mutagenic form of damage bypass during checkpoint silencing highlights the importance of keeping the checkpoint quiet during an early embryonic damage response, as the embryo essentially trades mutations for continued progression through the cell cycle. Thus embryos appear to violate one of the 10 biological commandments, but by doing so they keep their cell cycles "on the clock" and thereby survive the damage crisis—even if their genomes look a little different for having done so.