Cell cycle control of cohesion establishment

Cohesion between sister chromatids ensures accurate alignment and segregation of chromosomes during cell division. Cohesion establishment requires modification of the SMC3 subunit of cohesin by the ESCO2 acetyltransferase. ESCO2 function relies on interactions between ESCO2 and the DNA replication machinery, but how and whether these interactions are regulated during cell cycle progression is not known. Here we have found that phosphorylation of ESCO2 at serine 75 by cyclin-dependent kinase strongly impacts both interaction of ESCO2 with the replication machinery and ESCO2’s ability to ensure sister chromatid cohesion. This study provides mechanistic insight into how establishment of sister chromatid cohesion is entrained in S phase by cell cycle-dependent mechanisms.