RT Journal Article
SR Electronic
T1 Mitotic exit is controlled during anaphase by an Aurora B-Cyclin B1/Cdk1 crosstalk
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 606517
DO 10.1101/606517
A1 Olga Afonso
A1 Liam P. Cheeseman
A1 Luísa T. Ferreira
A1 Eurico Morais-de-Sá
A1 Helder Maiato
YR 2019
UL http://biorxiv.org/content/early/2019/04/12/606517.abstract
AB 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.