Cyclin B2/CDK1 inhibits separase activity in oocyte meiosis I

Abstract

Chromosome segregation is driven by separase, whose activity is inhibited by binding to securin and cyclin B1/CDK1. In meiosis, premature separase activity will induce aneuploidy or abolish chromosome segregation by untimely destroying cohesin. Recently, we have proved that cyclin B2 can compensate for cyclin B1 in CDK1 activation for the oocyte meiosis G2/M transition. In the present study, we identified the interaction between cyclin B2/CDK1 and separase. We found that cyclin B2 degradation was required for separase activation during metaphase I-anaphase I transition because stable cyclin B2 led to failure of homologous chromosome separation and metaphase I arrest, especially in the simultaneous absence of securin and cyclin B1. Moreover, non-phosphorylatable separase rescued the separation of homologous chromosomes in the stable cyclin B2-arrested cyclin B1-null oocytes. Our results indicate that cyclin B2/CDK1 is also responsible for separase inhibition via inhibitory phosphorylation to regulate chromosome separation in oocyte meiosis, which may not occur in other cell types.