Deepak Adhikari1, M. Kasim Diril2, Kiran Busayavalasa1, Sanjiv Risal1, Shoma Nakagawa3, Rebecca Lindkvist1, Yan Shen1, Vincenzo Coppola4, Lino Tessarollo4, Nobuaki R. Kudo3, Philipp Kaldis2,5,*, and Kui Liu1,*
* corresponding authors
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
Published in Journal of Cell Biology, 206, 843-853 on 22 September 2014.
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In mitosis, the Greatwall kinase (called microtubuleassociated 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.
Figure Legend: Meiotic maturation of OoMastl-/-oocytes.
Representative images of immunostaining for DNA, CREST, and spindle showing normal progression to metaphase I in OoMastl-/- oocytes. Oocytes were cultured for the indicated periods after GVBD and were fixed. 30 oocytes were analyzed for each time point.
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