Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase transition irreversible
Rattani A., Vinod PK., Godwin J., Tachibana-Konwalski K., Wolna M., Malumbres M., Novák B., Nasmyth K.
Activation of anaphase-promoting complex/cyclosome (APC/CCdc20) by Cdc20 is delayed by the spindle assembly checkpoint (SAC). When all kinetochores come under tension, the SAC is turned off and APC/CCdc20degrades cyclin B and securin, which activates separase . The latter then cleaves cohesin holding sister chromatids together . 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/CCdc20activates separase but the resulting loss of (some) cohesion is accompanied by SAC reactivation and APC/CCdc20inhibition, which aborts the process of further securin degradation. Cyclin B is therefore the only APC/CCdc20substrate 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. © 2014 The Authors.