Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion.
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.
Rolef Ben-Shahar
Tom
T
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln'sInn Fields, London WC2A 3PX, UK.
Heeger
Sebastian
S
Lehane
Chris
C
East
Philip
P
Flynn
Helen
H
Skehel
Mark
M
Uhlmann
Frank
F
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
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