Eco1-Dependent Cohesin Acetylation During Establishment of Sister Chromatid Cohesion

• DOI: 10.1126/science.1157774
• Publication Date: 2008-07-24T21:24:54Z
• Authors: Tom Rolef Ben-Shahar; Sebastian Heeger; Chris Lehane; Philip East; Helen Flynn; Mark Skehel; Frank Uhlmann
• Keywords: DNA Replication; 0303 health sciences; Saccharomyces cerevisiae Proteins; DNA Repair; Chromosomal Proteins, Non-Histone; Nuclear Proteins; Acetylation; Cell Cycle Proteins; Saccharomyces cerevisiae; Chromatids; S Phase; Protein Subunits; 03 medical and health sciences; Suppression, Genetic; Chondroitin Sulfate Proteoglycans; Acetyltransferases; Mutation; Chromosomes, Fungal; DNA, Fungal; Alleles

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.