TY - JOUR TI - The CDK Pef1 and protein phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes AU - Birot, Adrien AU - Tormos-Pérez, Marta AU - Vaur, Sabine AU - Feytout, Amélie AU - Jaegy, Julien AU - Alonso Gil, Dácil AU - Vazquez, Stéphanie AU - Ekwall, Karl AU - Javerzat, Jean-Paul A2 - Stillman, Bruce A2 - Manley, James L A2 - Stillman, Bruce VL - 9 PY - 2020 DA - 2020/01/02 SP - e50556 C1 - eLife 2020;9:e50556 DO - 10.7554/eLife.50556 UR - https://doi.org/10.7554/eLife.50556 AB - 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. KW - cohesin KW - Phosphatase KW - CDK KW - cohesion KW - loop extrusion KW - S. pombe JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -