Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase transition irreversible

Curr Biol. 2014 Mar 17;24(6):630-7. doi: 10.1016/j.cub.2014.01.033. Epub 2014 Feb 27.


Activation of anaphase-promoting complex/cyclosome (APC/C(Cdc20)) by Cdc20 is delayed by the spindle assembly checkpoint (SAC). When all kinetochores come under tension, the SAC is turned off and APC/C(Cdc20) degrades cyclin B and securin, which activates separase [1]. The latter then cleaves cohesin holding sister chromatids together [2]. Because cohesin cleavage also destroys the tension responsible for turning off the SAC, cells must possess a mechanism to prevent SAC reactivation during anaphase, which could be conferred by a dependence of the SAC on Cdk1 [3-5]. To test this, we analyzed mouse oocytes and embryos expressing nondegradable cyclin B together with a Cdk1-resistant form of separase. After biorientation and SAC inactivation, APC/C(Cdc20) activates separase but the resulting loss of (some) cohesion is accompanied by SAC reactivation and APC/C(Cdc20) inhibition, which aborts the process of further securin degradation. Cyclin B is therefore the only APC/C(Cdc20) substrate whose degradation at the onset of anaphase is necessary to prevent SAC reactivation. The mutual activation of tension sensitive SAC and Cdk1 creates a bistable system that ensures complete activation of separase and total downregulation of Cdk1 when all chromosomes have bioriented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / physiology*
  • Animals
  • CDC2 Protein Kinase / physiology*
  • Cdc20 Proteins / physiology
  • Chromatids / physiology
  • Cyclin B / physiology
  • Female
  • M Phase Cell Cycle Checkpoints / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Nondisjunction, Genetic / physiology
  • Oocytes / physiology
  • Phosphorylation


  • Cdc20 Proteins
  • Cyclin B
  • CDC2 Protein Kinase