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Curr Biol. 2017 May 22;27(10):1462-1476.e5. doi: 10.1016/j.cub.2017.04.023. Epub 2017 May 11.

APC/CCdh1 Enables Removal of Shugoshin-2 from the Arms of Bivalent Chromosomes by Moderating Cyclin-Dependent Kinase Activity.

Author information

1
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
2
Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne NE1 4EP, UK; Wellcome Trust Centre for Mitochondrial Research, Institute for Genetic Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
3
Cell Division and Cancer Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
4
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
5
Instituto de Biología Molecular y Celular del Cáncer de Salamanca, CSIC-Universidad de Salamanca, 37007 Salamanca, Spain.
6
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: ashley.nasmyth@bioch.ox.ac.uk.

Abstract

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.

KEYWORDS:

APC/C(Cdh1); aneuploidy; aurora kinase; cohesin; meiosis; shugoshin-2

PMID:
28502659
PMCID:
PMC5457479
DOI:
10.1016/j.cub.2017.04.023
[Indexed for MEDLINE]
Free PMC Article

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