Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk
Olga Afonso,
Colleen M Castellani,
Liam P Cheeseman,
Jorge G Ferreira,
Bernardo Orr,
Luisa T Ferreira,
James J Chambers,
Eurico Morais-de-Sá,
Thomas J Maresca,
Helder Maiato
Affiliations
Olga Afonso
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
Colleen M Castellani
Biology Department, University of Massachusetts, Amherst, United States
Liam P Cheeseman
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
Jorge G Ferreira
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
Bernardo Orr
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
Luisa T Ferreira
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
James J Chambers
Institute for Applied Life Sciences, University of Massachusetts, Amherst, United States
Eurico Morais-de-Sá
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
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; Cell Division Group, Experimental Biology Unit, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
According 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.
