Mitotic exit is controlled during anaphase by an Aurora B-Cyclin B1/Cdk1 crosstalk

Abstract

According to the prevailing \"clock\" model, chromosome decondensation and nuclear envelope reassembly during mitotic exit are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient - the \"ruler\" model. Here we reconciled both models by showing that Cyclin B1 degradation continues during anaphase in Drosophila, mouse and human cells, including primary tissues. This required APC/CCdh1 activity, and failure to degrade Cyclin B1 during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1 localization and half-life during anaphase depended on kinesin-6, which targets Aurora B to the spindle midzone. Mechanistically, we show that anaphase duration is regulated by Aurora B-mediated phosphorylation of Cyclin B1. We propose that a crosstalk between molecular \"rulers\" and \"clocks\" licenses mitotic exit only after proper chromosome separation.