Hos1 is a lysine deacetylase for the Smc3 subunit of cohesin.

Chromosome cohesion is a cell-cycle-regulated process in which sister chromatids are held together from the time of replication until the time of separation at the metaphase-to-anaphase transition, ensuring accurate chromosome segregation [1-9]. Chromosome cohesion is established during S phase, and this process requires the four subunits of the cohesin complex (Smc1, Smc3, Mcd1/Scc1, and Irr1/Scc3) and the acetyltransferase Eco1 [10-13]. Acetylation of Smc3 by Eco1 at two evolutionarily conserved lysine residues promotes cohesion establishment during S phase in budding yeast and humans [14-16]. Here we report that Hos1, a member of the evolutionarily conserved class I histone deacetylase family, acts as a deacetylase for Smc3 in S. cerevisiae. We examine the Smc3 acetylation level in nine histone deacetylase deletion strains and find that the acetylation level is increased specifically in a hos1Δ strain post-S phase. Coimmunoprecipitation experiments show that Hos1 interacts with Smc3 and that the interaction is most pronounced as cells reach anaphase. We provide direct evidence that Hos1 can deacetylate Smc3 and retains a soluble pool of deacetylated Smc3. Overexpression of Hos1 results in less acetylation of Smc3 and cohesion defects in both WT and eco1 mutant strains; mutation of the Hos1 active site abolishes the defects. Hos1 may help to maintain a pool of unacetylated Smc3 that can be used for new chromosome cohesion.