RNF212, a SUMO E3 Ligase, Impedes DNA Break Repair to Enable Oocyte Quality Control
Oocyte quality control culls eggs with defects in meiosis. In mouse, postnatal oocyte death is triggered by defects in chromosome synapsis and recombination, both of which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. My lab is interested in the roles of post-translational modification, Ubiquitination and SUMOylation, in meiotic checkpoints. We found that RNF212, a SUMO E3-ligase required for crossing over, also functions in oocyte quality control. Both physiological apoptosis and the wholesale elimination of oocytes seen in meiotic mutants require RNF212. Analysis of DNA damage repair implies that RNF212 impedes DSB repair as chromosomes desynapse, likely by blocking recombination between sister chromatids. Consistently, HORMAD1, a negative regulator of inter-sister recombination, requires RNF212 for its association with desynapsing chromosomes. We infer that by blocking repair of residual DSBs, oocytes retain a “memory” of defective inter-homolog interactions that enables quality control processes. Together, these results define the logic of postnatal oocyte quality control and suggest that RNF212 variants may influence the transmission of defective genomes.