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Aneuploidy in oocytes is prevented by sustained CDK1 activity through degron masking in cyclin B1

Lookup NU author(s): Dr Mark Levasseur, Christopher Thomas, Dr Owen Davies, Professor Jonathan Higgins, Dr Suzanne Madgwick

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


Abstract

Successful mitosis requires that cyclin B1:CDK1 kinase activity remains high until chromosomes are correctly aligned on the mitotic spindle. It has therefore been unclear why, in mammalian oocyte meiosis, cyclin B1 destruction begins before chromosome alignment is complete. Here we resolve this paradox and show that mouse oocytes exploit an imbalance in the ratio of cyclin B1 to CDK1 to control CDK1 activity; early cyclin B1 destruction reflects the loss of an excess of non-CDK1 bound cyclin B1 in late prometaphase, while CDK1-bound cyclin B1 is only destroyed during metaphase. The ordered destruction of the two forms of cyclin B1 is brought about by a previously unidentified motif which is accessible in free cyclin B1, but masked when cyclin B1 is in complex with CDK1. This protects the CDK1-bound fraction from destruction in prometaphase, ensuring a period of prolonged CDK1 activity sufficient to achieve optimal chromosome alignment and prevent aneuploidy.


Publication metadata

Author(s): Levasseur MD, Thomas C, Davies OR, Higgins JMG, Madgwick S

Publication type: Article

Publication status: Published

Journal: Developmental Cell

Year: 2019

Volume: 48

Pages: 1-18

Print publication date: 11/03/2019

Online publication date: 07/02/2019

Acceptance date: 29/12/2018

ISSN (print): 1534-5807

ISSN (electronic): 1878-1551

Publisher: Cell Press

URL: https://doi.org/10.1016/j.devcel.2019.01.008

DOI: 10.1016/j.devcel.2019.01.008


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