Cyclin A2 Is Required for Sister Chromatid Segregation, But Not Separase Control, in Mouse Oocyte Meiosis

SummaryIn meiosis, two specialized cell divisions allow the separation of paired chromosomes first, then of sister chromatids. Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. Using mouse oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role; namely, its requirement for separase-dependent sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase activity in meiosis I leads to precocious sister separation, whereas inhibition of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Cyclin A2 is required for meiotic entry and sister chromatid separation in meiosis II ► Constitutive cyclin A2 activity in meiosis I leads to precocious sister separation ► Only cyclin B1, and not cyclin A2, can inhibit separase in mouse oocyte meiosis I ► Endogenous cyclin A is localized to centromeres throughout the second meiotic division