Mechanisms of quality control differ in male and female germ cells

Despite the high importance of protecting the genome in the germline, paradoxically, hundreds of DNA double strand breaks (DSBs) are generated by SPO11, in meiotic germ cells. These DSBs serve an important function as they initiate meiotic homologous recombination which is not only necessary to repair the DSBs, but also to promote the pairing of homologous chromosomes. At least one repair event per chromosome pair creates crossovers which is required for reliable chromosome segregation during cell division. Given that efficient repair of high numbers of DSBs is not straightforward, some of the meiotic germ cells fail to repair all of the SPO11-induced DSBs. Oocytes with persistent DSBs are eliminated by apoptosis before entering dictyate arrest, which is a resting stage of oocytes that can last up to 50 years in humans. The oocyte surveillance system that triggers cell death in response to DSBs has been characterized in recent years. It involves a member of the p53 protein family, TAp63α, that is preferentially produced in resting oocytes [ 1 ]. This p63 isoform adopts an inactive and only dimeric conformation [ 2 ]. ATM- and/or ATR-mediated detection of DSBs activates the DNA damage response kinase CHK2, which phosphorylates TAp63α at S582 [ 3 ]. While this phosphorylation is not sufficient to activate TAp63α, it recruits the kinase CK1 [ 4 ]. Sequential addition of four more phosphate groups results in activation of TAp63α to the tetrameric state [ 5 ] and initiation of apoptosis [ 6 ].