Replication continues in DNA-damaged embryos (top) unless translesion synthesis is blocked (bottom).

On page 999, Holway et al. reveal that worm embryos would rather risk genomic mutation than disturb the timing of cell division. DNA damage–induced checkpoints, the group finds, are silenced during early embryogenesis.

The need for the silencing arises because of the importance of timing in embryogenesis. At the worm's two-cell stage, for instance, a two-minute lag between the division times of the two cells is needed for germ line formation. Embryogenesis fails if this lag is extended, as would be expected upon DNA damage.

Holway and colleagues found, however, that genomic damage from UV or MMS treatments did not stall division in worm embryos. In somatic cells, DNA lesions block the progress of replication forks, whose stalling initiates the damage checkpoint. But replication forks advanced directly through the lesions in the embryos. This bypass required a translesion polymerase called Polh-1, which is able to synthesize DNA opposite damaged bases. The high expression levels of Polh-1 in embryos might at least partly explain their unusual ability to silence the checkpoint.

Fly and frog embryos do not actively silence the DNA damage checkpoint; mammalian systems have not yet been tested. Based on these findings, however, one might speculate that tumor cells that are resistant to chemotherapy might have acquired a heightened capacity for translesion synthesis.