The CDK Pef1 and Protein Phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes

  1. Adrien Birot
  2. Marta Tormos-Pérez
  3. Sabine Vaur
  4. Amélie Feytout
  5. Julien Jaegy
  6. Dácil Alonso Gil
  7. Stéphanie Vazquez
  8. Karl Ekwall
  9. Jean-Paul Javerzat  Is a corresponding author
  1. CNRS-Université de Bordeaux, France
  2. Karolinska Institute, Sweden

Abstract

Cohesin has essential roles in chromosome structure, segregation and repair. Cohesin binding to chromosomes is catalyzed by the cohesin loader, Mis4 in fission yeast. How cells fine tune cohesin deposition is largely unknown. Here we provide evidence that Mis4 activity is regulated by phosphorylation of its cohesin substrate. A genetic screen for negative regulators of Mis4 yielded a CDK called Pef1, whose closest human homologue is CDK5. Inhibition of Pef1 kinase activity rescued cohesin loader deficiencies. In an otherwise wild-type background, Pef1 ablation stimulated cohesin binding to its regular sites along chromosomes while ablating Protein Phosphatase 4 had the opposite effect. Pef1 and PP4 control the phosphorylation state of the cohesin kleisin Rad21. The CDK phosphorylates Rad21 on Threonine 262. Pef1 ablation, non phosphorylatable Rad21-T262 or mutations within a Rad21 binding domain of Mis4 alleviated the effect of PP4 deficiency. Such a CDK/PP4 based regulation of cohesin loader activity could provide an efficient mechanism for translating cellular cues into a fast and accurate cohesin response.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1, 2, 4, 6 and 7

Article and author information

Author details

  1. Adrien Birot

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Marta Tormos-Pérez

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Sabine Vaur

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Amélie Feytout

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Julien Jaegy

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Dácil Alonso Gil

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Stéphanie Vazquez

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Karl Ekwall

    Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  9. Jean-Paul Javerzat

    Institut de Biochimie et Génétique Cellulaires, CNRS-Université de Bordeaux, Bordeaux, France
    For correspondence
    jpaul.javerzat@ibgc.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9671-6753

Funding

Fondation ARC pour la Recherche sur le Cancer (PJA 2013 1200 205)

  • Jean-Paul Javerzat

Fondation ARC pour la Recherche sur le Cancer (PJA 20171206211)

  • Jean-Paul Javerzat

Agence Nationale de la Recherche (ANR-14-CE10-0020-01)

  • Jean-Paul Javerzat

Agence Nationale de la Recherche (ANR-10-IDEX-03-02)

  • Adrien Birot

Fondation ARC pour la Recherche sur le Cancer (DOC20160603884)

  • Adrien Birot

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

Reviewing Editor

  1. Bruce Stillman, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: July 25, 2019
  2. Accepted: January 2, 2020
  3. Accepted Manuscript published: January 2, 2020 (version 1)
  4. Version of Record published: January 10, 2020 (version 2)

Copyright

© 2020, Birot 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. Adrien Birot
  2. Marta Tormos-Pérez
  3. Sabine Vaur
  4. Amélie Feytout
  5. Julien Jaegy
  6. Dácil Alonso Gil
  7. Stéphanie Vazquez
  8. Karl Ekwall
  9. Jean-Paul Javerzat
(2020)
The CDK Pef1 and Protein Phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes
eLife 9:e50556.
https://doi.org/10.7554/eLife.50556

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