Trading Accuracy for Speed

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Science  07 Apr 2006:
Vol. 312, Issue 5770, pp. 22
DOI: 10.1126/science.312.5770.22b

Genetic damage is potentially very dangerous to cells, so when it does occur, repair usually follows right away. During cell division, DNA replication forks grind to a halt at sites of damage, activating a “checkpoint” that delays cell-cycle progression until repair is complete. But for some developmental processes, cell-cycle timing is itself critical, as in the asynchronous cell divisions that occur in the two-cell Caenorhabditis elegans embryo. How do developing nematodes keep to schedule when confronted by a checkpoint?

Holway et al. show that during early C. elegans embryonic development, checkpoint activation by damaged DNA is prevented by the genes rad2 and gei-17 but remains responsive to developmental inputs that regulate timing. gei-17 suppresses the repair checkpoint by facilitating replication through damaged DNA. Although the normal replication machinery cannot cope with damaged DNA, the so-called translesion DNA polymerase polh-1 enables the C. elegans embryo to overcome genomic damage and avoid a fatal delay in cell division. But this is a tradeoff: Translesion polymerases are error-prone, and embryos opt for survival at the cost of an increase in mutations. — GR

J. Cell Biol. 172, 999 (2006).

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