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.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Helder Maiato
- Helder Maiato
- Liam P Cheeseman
- Eurico Morais-de-Sá
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All mice were maintained in a specific pathogen-free environment according to the Portuguese animal welfare authority regulations (Direcção Geral de Alimentação e Veterinária; reference# 0421/000/000/2016) and the guidelines of the Instituto de Investigação e Inovação em Saúde animal facility.
- Jon Pines, Institute of Cancer Research Research, United Kingdom
© 2019, Afonso et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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