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APC/C^Cdh1 Enables Removal of Shugoshin-2 from the Arms of Bivalent Chromosomes by Moderating Cyclin-Dependent Kinase Activity

Lookup NU author(s): Dr Randy Ballesteros Mejia, Professor Mary Herbert

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2017 The Authors. In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/CCdc20) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin. We show here that, by promoting proteolysis of cyclins and Cdc25B at the germinal vesicle (GV) stage, APC/C associated with the Cdh1 protein (APC/CCdh1) delays the increase in Cdk1 activity, leading to germinal vesicle breakdown (GVBD). More surprisingly, by moderating the rate at which Cdk1 is activated following GVBD, APC/CCdh1 creates conditions necessary for the removal of shugoshin-2 from chromosome arms by the Aurora B/C kinase, an event crucial for the efficient resolution of chiasmata. Rattani et al. report that the APC/CCdh1 moderates the rise in Cdk1 activity as mouse oocytes resume meiosis. This creates a window of low Cdk1 activity shortly after GVBD, which promotes Aurora B/C kinase-dependent removal of shugoshin-2 from chromosome arms, failure of which could result in aneuploidy at the first meiotic division.

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Author(s): Rattani A, Ballesteros Mejia R, Roberts K, Roig MB, Godwin J, Hopkins M, Eguren M, Sanchez-Pulido L, Okaz E, Ogushi S, Wolna M, Metson J, Pendas AM, Malumbres M, Novak B, Herbert M, Nasmyth K

Publication type: Article

Publication status: Published

Journal: Current Biology

Year: 2017

Volume: 27

Issue: 10

Pages: 1462-1476

Print publication date: 22/05/2017

Online publication date: 11/05/2017

Acceptance date: 12/04/2017

Date deposited: 11/07/2017

ISSN (print): 0960-9822

Publisher: Cell Press

URL: http://doi.org/10.1016/j.cub.2017.04.023

DOI: 10.1016/j.cub.2017.04.023

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