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

Mark D. Levasseur, Christopher Thomas, Owen R. Davies, Jonathan M.G. Higgins, Suzanne Madgwick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 destroyed only during metaphase. The ordered destruction of the two forms of cyclin B1 is brought about by a previously unidentified motif that 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.

Original languageEnglish
Pages (from-to)672-684.e5
Number of pages13
JournalDevelopmental Cell
Volume48
Issue number5
DOIs
Publication statusPublished - 11 Mar 2019

Keywords

  • aneuploidy
  • APC/C
  • Cdc20
  • chromosome segregation
  • cyclin B1
  • degron
  • meiosis
  • oocyte
  • proteostasis
  • spindle checkpoint

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