Esco1 and Esco2 regulate distinct cohesin functions during cell cycle progression

Significance Sister chromatids are tethered together by the cohesin complex from the time they are made until cell division. Acetylation of the Smc3 subunit of cohesin stabilizes its association with chromatin, and is critical for sister chromatid cohesion. In vertebrates, cohesin is acetylated by two related enzymes: Esco1 and Esco2. We show here that Esco1 is responsible for most Smc3 acetylation but has very little effect on sister cohesion. Esco1 is active throughout the cell cycle, while Esco2 modifies cohesin only during S phase, when sister chromatid cohesion is established. We propose that two distinct pathways regulate cohesin in vertebrates: one is dedicated to cohesion between sister chromatids, and one promotes other functions of cohesin, such as maintenance of chromosome structure.