Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion |
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Authors: | Rolef Ben-Shahar Tom Heeger Sebastian Lehane Chris East Philip Flynn Helen Skehel Mark Uhlmann Frank |
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Affiliation: | Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln'sInn Fields, London WC2A 3PX, UK. |
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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. |
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