The CDK Pef1 and Protein Phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes
- CNRS-Université de Bordeaux, France
- 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
Jean-Paul Javerzat
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.
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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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
