Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk

eLife

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[1] Biology Department, University of Massachusetts, Amherst, United States;Biology Department, University of Massachusetts, Amherst, United States;Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, United States;Chromosome Instability & Dynamics Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;Chromosome Instability & Dynamics Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;Cell Division Group, Experimental Biology Unit, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Porto, Portugal;Institute for Applied Life Sciences, University of Massachusetts, Amherst, United States;Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;Epithelial Polarity & Cell Division Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;

关键词: mitosis;    anaphase;    Aurora B;    Cyclin B1;    Cdk1;    mitotic exit;    Human;    Mouse;    D. melanogaster;   

DOI  :  10.7554/eLife.47646

来源: publisher

【 摘 要 】

10.7554/eLife.47646.001According to the prevailing ‘clock’ model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis 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 found that Cdk1 remains active during anaphase due to ongoing APC/CCdc20- and APC/CCdh1-mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular ‘rulers’ and ‘clocks’ licenses mitotic exit only after proper chromosome separation.

【 授权许可】

CC BY