Aneuploidy in Oocytes Is Prevented by Sustained CDK1 Activity through Degron Masking in CyclinB1

Successful mitosis requires that cyclin B1:CDK1 ki-nase activity remains high until chromosomes arecorrectly aligned on the mitotic spindle. It has there-fore been unclear why, in mammalian oocytemeiosis, cyclin B1 destruction begins before chro-mosome alignment is complete. Here, we resolvethis paradox and show that mouse oocytes exploitan imbalance in the ratio of cyclin B1 to CDK1 to con-trol CDK1 activity; early cyclin B1 destruction reflectsthe loss of an excess of non-CDK1-bound cyclin B1in late prometaphase, while CDK1-bound cyclin B1is destroyed only during metaphase. The ordereddestruction of the two forms of cyclin B1 is broughtabout by a previously unidentified motif that isaccessible in free cyclin B1 but masked when cyclinB1 is in complex with CDK1. This protects the CDK1-bound fraction from destruction in prometaphase,ensuring a period of prolonged CDK1 activity suffi-cient to achieve optimal chromosome alignmentand prevent aneuploidy.