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bioRxiv · 10.1101/606517

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

Maiato, H.·Afonso, O.·Cheeseman, L.·Ferreira, L.·Morais-de-Sa, E.
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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.

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Maiato, H., Afonso, O., Cheeseman, L., Ferreira, L., Morais-de-Sa, E.. 2019-04-12. Mitotic exit is controlled during anaphase by an Aurora B-Cyclin B1/Cdk1 crosstalk. https://doi.org/10.1101/606517

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