Eco1-Dependent Cohesin Acetylation During Establishment of Sister Chromatid Cohesion

• Published in: Science (American Association for the Advancement of Science) Vol. 321; no. 5888; pp. 563 - 566
• Main Authors: Ben-Shahar, Tom Rolef, Heeger, Sebastian, Lehane, Chris, East, Philip, Flynn, Helen, Skehel, Mark, Uhlmann, Frank
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 25-07-2008; The American Association for the Advancement of Science
• Subjects: Acetylation; Acetyltransferases - chemistry; Acetyltransferases - genetics; Acetyltransferases - metabolism; Alleles; Biochemistry; Biological and medical sciences; Biomedical research; Cell cycle; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chemical synthesis; Chondroitin Sulfate Proteoglycans - chemistry; Chondroitin Sulfate Proteoglycans - genetics; Chondroitin Sulfate Proteoglycans - metabolism; Chromatids; Chromatids - physiology; Chromosomal Proteins, Non-Histone - chemistry; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes, Fungal - physiology; Complementation; Diploidy; DNA Repair; DNA Replication; DNA, Fungal - metabolism; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genetics; Interphase; Molecular and cellular biology; Molecular genetics; Mutation; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; Replication; S Phase; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Saccharomycetales; Suppression, Genetic; Chromatid; Cohesion; Replication; Acetylation; DNA
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1157774

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.