title: Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion.
abstract: Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward. This requires the replication fork-associated acetyl transferase Eco1, but Eco1's mechanism of action is not known. We identified spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast. An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion. A second set of eco1-1 suppressors inactivate the budding yeast ortholog of the cohesin destabilizer Wapl. Our results indicate that Eco1 modifies cohesin to stabilize sister chromatid cohesion in parallel with a cohesion establishment reaction that is in principle Eco1-independent.
authors.affiliation: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln'sInn Fields, London WC2A 3PX, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Rolef Ben-Shahar
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heeger
authors.forename: Chris
authors.initials: C
authors.lastname: Lehane
authors.forename: Philip
authors.initials: P
authors.lastname: East
authors.forename: Helen
authors.initials: H
authors.lastname: Flynn
authors.forename: Mark
authors.initials: M
authors.lastname: Skehel
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000502:physiology*; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic
chemical_list: D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D009687:Nuclear Proteins; D021122:Protein Subunits; C476199:RAD61 protein, S cerevisiae; C120372:SMC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C118076:ECO1 protein, S cerevisiae