Trouble in transitioning: activation of zygotic transcription can lead to DNA breakage and genome instability.

Recent work from our laboratory has identified zygotic genome activation as a source of intrinsic DNA damage during germline development in C. elegans. More specifically, we have found that the primordial germ cells Z2 and Z3 experience DNA damage and damage checkpoint activation shortly after RNA polymerase II is activated by a nutrient-dependent signal in L1 stage animals. In this Commentary we review these data, put them into context with other examples of programmed DNA double-strand breaks (DSBs) during gene activation, and speculate as to how a DSB would facilitate signal-dependent activation of gene expression.