Spatiotemporal control of mitotic exit during anaphase by an Aurora B-Cdk1 crosstalk
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
- University of Massachusetts, United States
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
European Reseach Council (681443)
- Helder Maiato
Fundação Luso-Americana (FLAD LifeScience2020)
- Helder Maiato
Marie Skłodowska-Curie Action (746515)
- Liam P Cheeseman
Fundação para a Ciência e a Tecnologia (PTDC/BEX-BCM/0432/2014)
- 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.
Reviewing Editor
- Jon Pines, Institute of Cancer Research Research, United Kingdom
Ethics
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.
Version history
- Received: April 11, 2019
- Accepted: August 10, 2019
- Accepted Manuscript published: August 19, 2019 (version 1)
- Version of Record published: August 22, 2019 (version 2)
Copyright
© 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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Spatiotemporal control of mitotic exit during anaphase by an Aurora B-Cdk1 crosstalk
eLife 8:e47646.
https://doi.org/10.7554/eLife.47646
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