APC/CCdh1 Enables Removal of Shugoshin-2 from the Arms of Bivalent Chromosomes by Moderating Cyclin-Dependent Kinase Activity

In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/CCdc20) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin. We show here that, by promoting proteolysis of cyclins and Cdc25B at the germinal vesicle (GV) stage, APC/C associated with the Cdh1 protein (APC/CCdh1) delays the increase in Cdk1 activity, leading to germinal vesicle breakdown (GVBD). More surprisingly, by moderating the rate at which Cdk1 is activated following GVBD, APC/CCdh1 creates conditions necessary for the removal of shugoshin-2 from chromosome arms by the Aurora B/C kinase, an event crucial for the efficient resolution of chiasmata. [Display omitted] •Sgol2 phosphorylation by Aurora B/C kinase dissociates it from chromosome arms•APC/CCdh1 ensures a gradual increase in Cdk1 activity at the resumption of meiosis•APC/CCdh1 activity enables Aurora B/C kinase-dependent Sgol2 phosphorylation•By promoting Sgol2 removal from chromosome arms, APC/CCdh1 prevents non-disjunction Rattani et al. report that the APC/CCdh1 moderates the rise in Cdk1 activity as mouse oocytes resume meiosis. This creates a window of low Cdk1 activity shortly after GVBD, which promotes Aurora B/C kinase-dependent removal of shugoshin-2 from chromosome arms, failure of which could result in aneuploidy at the first meiotic division.