Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II

Deepak Adhikari, M. Kasim Diril, Kiran Busayavalasa, Sanjiv Risal, Shoma Nakagawa, Rebecca Lindkvist, Yan Shen, Vincenzo Coppola, Lino Tessarollo, Nobuaki R. Kudo, Philipp Kaldis, Kui Liu

In mitosis, the Greatwall kinase (called microtubule-associated serine/threonine kinase like [Mastl] in mammals) is essential for prometaphase entry or progression by suppressing protein phosphatase 2A (PP2A) activity. PP2A suppression in turn leads to high levels of Cdk1 substrate phosphorylation. We have used a mouse model with an oocyte-specific deletion of Mastl to show that Mastl-null oocytes resume meiosis I and reach metaphase I normally but that the onset and completion of anaphase I are delayed. Moreover, after the completion of meiosis I, Mastl-null oocytes failed to enter meiosis II (MII) because they reassembled a nuclear structure containing decondensed chromatin. Our results show that Mastl is required for the timely activation of anaphase-promoting complex/cyclosome to allow meiosis I exit and for the rapid rise of Cdk1 activity that is needed for the entry into MII in mouse oocytes.