Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast

Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Ecol, a conserved acetyltransferase. However, due to the lack of known in vivo substrates, how Ecol regulates cohesion is not understood. Here we report that yeast Ecol and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues. Mutating these lysine residues to a nonacetylatable form leads to increased loss of sister chromatid cohesion and genome instability in both yeast and human. In addition, we clarified that the acetyltransferase activity of Ecol is essential for its function. Our study thus identified a molecular target for the acetyltransferase Ecol and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion.