Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Rattani A 

PROVIDER: S-EPMC3969274 | BioStudies | 2014-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3969148 | BioStudies
1000-01-01 | S-EPMC4400591 | BioStudies
1000-01-01 | S-EPMC2682603 | BioStudies
2014-01-01 | S-EPMC4195823 | BioStudies
1000-01-01 | S-EPMC3059483 | BioStudies
2008-01-01 | S-EPMC2636747 | BioStudies
1000-01-01 | S-EPMC3305350 | BioStudies
1000-01-01 | S-EPMC2635557 | BioStudies
1000-01-01 | S-EPMC4128882 | BioStudies
1000-01-01 | S-EPMC3780767 | BioStudies