Mis12 controls cyclin B1 stabilization via Cdc14B-mediated APC/CCdh1 regulation during meiotic G2/M transition in mouse oocytes.

Mammalian oocytes are arrested at G2/prophase of the first meiosis. After a hormone surge, oocytes resume meiosis, undergoing germinal vesicle breakdown (GVBD). This process is regulated by Cdk1/cyclin B1. Here, we report that Mis12 is required for G2/M transition by regulating cyclin B1 accumulation via Cdc14B-mediated APC/CCdh1 regulation, but is not essential for spindle and chromosome dynamics during meiotic maturation. Depletion of Mis12 severely compromised GVBD by impairing cyclin B1 accumulation. Importantly, impaired GVBD after Mis12 depletion was rescued not only by overexpressing cyclin B1 but also by depleting Cdc14B or Cdh1. Notably, oocytes rescued by cyclin B1 overexpression exhibited normal spindle and chromosome organization with intact kinetochore-microtubule attachments. In addition, after being rescued by cyclin B1 overexpression, Mis12-depleted oocytes normally extruded polar bodies. Moreover, Mis12-depleted oocytes formed pronuclear structures after fertilization but failed to develop beyond zygotes. Interestingly, Mis12 was localized in the cytoplasm and spindle poles in oocytes, in contrast to kinetochore localization in somatic cells. Therefore, our results demonstrate that Mis12 is required for meiotic G2/M transition but is dispensable for meiotic progression through meiosis I and II.