title: Hos1 is a lysine deacetylase for the Smc3 subunit of cohesin.
abstract: 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.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiong
authors.forename: Shuai
authors.initials: S
authors.lastname: Lu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gerton
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006655:Histone Deacetylases; D008239:Lysine; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C120372:SMC3 protein, S cerevisiae