Meiotic Errors Activate Checkpoints that Improve Gamete Quality without Triggering Apoptosis in Male Germ Cells

SummaryBackgroundMeiotic checkpoints ensure the production of gametes with the correct complement and integrity of DNA; in metazoans, these pathways sense errors and transduce signals to trigger apoptosis to eliminate damaged germ cells. The extent to which checkpoints monitor and safeguard the genome differs between sexes and may contribute to the high frequency of human female meiotic errors. In the C. elegans female germline, DNA damage, chromosome asynapsis, and/or unrepaired meiotic double-strand breaks (DSBs) activate checkpoints that induce apoptosis; conversely, male germ cells do not undergo apoptosis.ResultsHere we show that the recombination checkpoint is in fact activated in male germ cells despite the lack of apoptosis. The 9-1-1 complex and the phosphatidylinositol 3-kinase-related protein kinase ATR, sensors of DNA damage, are recruited to chromatin in the presence of unrepaired meiotic DSBs in both female and male germlines. Furthermore, the checkpoint kinase CHK-1 is phosphorylated and the p53 ortholog CEP-1 induces expression of BH3-only proapoptotic proteins in germlines of both sexes under activating conditions. The core cell death machinery is expressed in female and male germlines; however, CED-3 caspase is not activated in the male germline. Although apoptosis is not triggered, checkpoint activation in males has functional consequences for gamete quality, because there is reduced viability of progeny sired by males with a checkpoint-activating defect in the absence of checkpoint function.ConclusionsWe propose that the recombination checkpoint functions in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in the absence of apoptosis.

► Unlike C. elegans females, no checkpoint-activated germline apoptosis occurs in males ► Checkpoint proteins are activated in male germ cells in response to errors ► The cell death executor caspase CED-3 does not become activated in the male germline ► Checkpoints promote fidelity of chromosome inheritance in male germ cells