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

  1. Olga Afonso
  2. Colleen M Castellani
  3. Liam P Cheeseman
  4. Jorge G Ferreira
  5. Bernardo Orr
  6. Luisa T Ferreira
  7. James J Chambers
  8. Eurico Morais-de-Sá
  9. Thomas J Maresca
  10. Helder Maiato  Is a corresponding author
  1. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
  2. 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

  1. Olga Afonso

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  2. Colleen M Castellani

    Biology Department, University of Massachusetts, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Liam P Cheeseman

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  4. Jorge G Ferreira

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  5. Bernardo Orr

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  6. Luisa T Ferreira

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  7. James J Chambers

    Institute for Applied Life Sciences,, University of Massachusetts, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Eurico Morais-de-Sá

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  9. Thomas J Maresca

    Biology Department, University of Massachusetts, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2214-8674
  10. Helder Maiato

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    For correspondence
    maiato@i3s.up.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6200-9997

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.

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.

Reviewing Editor

  1. Jon Pines, Institute of Cancer Research Research, United Kingdom

Version history

  1. Received: April 11, 2019
  2. Accepted: August 10, 2019
  3. Accepted Manuscript published: August 19, 2019 (version 1)
  4. 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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  1. Olga Afonso
  2. Colleen M Castellani
  3. Liam P Cheeseman
  4. Jorge G Ferreira
  5. Bernardo Orr
  6. Luisa T Ferreira
  7. James J Chambers
  8. Eurico Morais-de-Sá
  9. Thomas J Maresca
  10. Helder Maiato
(2019)
Spatiotemporal control of mitotic exit during anaphase by an Aurora B-Cdk1 crosstalk
eLife 8:e47646.
https://doi.org/10.7554/eLife.47646

Share this article

https://doi.org/10.7554/eLife.47646

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