Separase cleaves the kinetochore protein Meikin at the meiosis I/II transition

To generate haploid gametes, germ cells undergo two consecutive meiotic divisions requiring key changes to the cell division machinery. Here, we demonstrate that the protease separase rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin. Separase proteolysis does not inactivate Meikin but instead alters its function to create a distinct activity state. Full-length Meikin and the C-terminal Meikin separase cleavage product both localize to kinetochores, bind to Plk1 kinase, and promote Rec8 cleavage, but our results reveal distinct roles for these proteins in controlling meiosis. Mutations that prevent Meikin cleavage or that conditionally inactivate Meikin at anaphase I result in defective meiosis II chromosome alignment in mouse oocytes. Finally, as oocytes exit meiosis, C-Meikin is eliminated by APC/C-mediated degradation prior to the first mitotic division. Thus, multiple regulatory events irreversibly modulate Meikin activity during successive meiotic divisions to rewire the cell division machinery at two distinct transitions. [Display omitted] •The meiosis-specific kinetochore protein Meikin is cleaved by the protease separase•Preventing Meikin cleavage causes meiosis II chromosome alignment defects in oocytes•The C-terminal Meikin fragment retains key activities and is required for meiosis II•Meikin is eliminated by APC/C-mediated degradation at meiotic exit Meiosis requires the dramatic rewiring of the chromosome segregation machinery at each division. Maier et al. find that the critical meiosis-specific kinetochore protein, Meikin, is regulated at key meiotic transitions through separase-mediated proteolytic cleavage and ubiquitin-mediated degradation, to enable distinct activities during the two meiotic divisions.