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

Author:

Adhikari Deepak1,Diril M. Kasim2,Busayavalasa Kiran1,Risal Sanjiv1,Nakagawa Shoma3,Lindkvist Rebecca1,Shen Yan1,Coppola Vincenzo4,Tessarollo Lino4,Kudo Nobuaki R.3,Kaldis Philipp25,Liu Kui1

Affiliation:

1. Department of Chemistry and Molecular Biology, University of Gothenburg, S-405 30 Gothenburg, Sweden

2. Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Republic of Singapore

3. Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London W12 0NN, England, UK

4. National Cancer Institute, Mouse Cancer Genetics Program, National Cancer Institute–Frederick, Frederick, MD 21702

5. Department of Biochemistry, National University of Singapore, Singapore 117599, Republic of Singapore

Abstract

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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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