1. Cell Biology
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Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription

  1. Marco Novais-Cruz
  2. Maria Alba Abad
  3. Wilfred FJ van IJcken
  4. Niels Galjart
  5. A Arockia Jeyaprakash
  6. Helder Maiato  Is a corresponding author
  7. Cristina Ferrás  Is a corresponding author
  1. Universidade do Porto, Portugal
  2. University of Edinburgh, United Kingdom
  3. Erasmus Medical Center, Netherlands
Research Article
  • Cited 10
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Cite this article as: eLife 2018;7:e36898 doi: 10.7554/eLife.36898

Abstract

Recent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain a robust spindle assembly checkpoint (SAC) response. Here we used live-cell imaging of human cells, RNA-seq and qPCR to investigate the requirement for de novo transcription during mitosis. Under conditions of persistently unattached kinetochores, transcription inhibition with actinomycin D, or treatment with other DNA-intercalating drugs, delocalized the chromosomal passenger complex (CPC) protein Aurora B from centromeres, compromising SAC signalling and cell fate. However, we were unable to detect significant changes in mitotic transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on Aurora B centromeric localization, SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, mitotic progression, arrest, exit or death is determined by centromere structural integrity, rather than de novo transcription.

Data availability

Processed RNA-seq have been deposited and can be consulted athttps://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-6661

The following data sets were generated

Article and author information

Author details

  1. Marco Novais-Cruz

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria Alba Abad

    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Wilfred FJ van IJcken

    Centre for Biomics, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0421-8301
  4. Niels Galjart

    Department of Cell Biology, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. A Arockia Jeyaprakash

    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Helder Maiato

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, 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
  7. Cristina Ferrás

    Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
    For correspondence
    cristina.ferras@ibmc.up.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1134-7387

Funding

FEDER-Fundo Europeu de desenvolvimento Regional funds through the COMPETE 2020 (Norte-01-0145-FEDER-000029)

  • Cristina Ferrás

FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 (Norte-07-0124-FEDER-000003)

  • Cristina Ferrás

Fundação para a Ciência e a Tecnologia (EXPL/IF/00765/2014/CP1241/CT0003)

  • Cristina Ferrás

Fundação para a Ciência e a Tecnologia (FCT Investigator grant IF/00765/2014)

  • Cristina Ferrás

Fundação para a Ciência e a Tecnologia (FCT PhD grant SFRH/BD/117063/2016)

  • Marco Novais-Cruz

European Research Council (CODECHECK)

  • Helder Maiato

FLAD Life Science

  • Helder Maiato

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jon Pines, The Gurdon Institute, United Kingdom

Publication history

  1. Received: March 23, 2018
  2. Accepted: August 3, 2018
  3. Accepted Manuscript published: August 6, 2018 (version 1)
  4. Version of Record published: September 7, 2018 (version 2)

Copyright

© 2018, Novais-Cruz 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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