RT Journal Article
SR Electronic
T1 The CDK Pef1 and Protein Phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 748855
DO 10.1101/748855
A1 Adrien Birot
A1 Marta Tormos-Pérez
A1 Sabine Vaur
A1 Amélie Feytout
A1 Julien Jaegy
A1 Dácil Alonso Gil
A1 Stéphanie Vazquez
A1 Karl Ekwall
A1 Jean-Paul Javerzat
YR 2019
UL http://biorxiv.org/content/early/2019/08/28/748855.abstract
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.