The DNA damage response (DDR) is a crucial mechanism that helps protect germline genome integrity. When activated, the DDR promotes cell cycle arrest (to permit DNA repair where feasible) or apoptosis. However, little is known about how damage to somatic tissues might influence germ cell development. Here, Gautam Chandra Sarkar, Arnab Mukhopadhyay and colleagues show that cdk-12 depletion in Caenorhabditis elegans results in downregulation of DDR genes and renders both the germline and somatic tissues more vulnerable to DNA damage. This is consistent with the known role of CDK-12 in the mammalian DDR. Global depletion of cdk-12 in low insulin signalling conditions causes germ cell arrest during meiosis I, meaning that no oocytes are produced. Surprisingly, by targeting specific tissues, the authors show that this arrest is only promoted by cdk-12 depletion in the uterine tissues. Depletion of daf-16, a downstream target of insulin signalling, rescues germ cell arrest and allows oocyte production. However, these oocytes exhibit morphological defects indicative of a reduction in oocyte quality. Together, this work suggests that activation of DAF-16 may help promote germ cell cycle arrest in response to somatic DNA damage.
