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Science 25 July 2008:
Vol. 321. no. 5888, pp. 563 - 566
DOI: 10.1126/science.1157774
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Reports

Eco1-Dependent Cohesin Acetylation During Establishment of Sister Chromatid Cohesion

Tom Rolef Ben-Shahar,1* Sebastian Heeger,1* Chris Lehane,1* Philip East,2 Helen Flynn,3 Mark Skehel,3 Frank Uhlmann1{dagger}

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.

1 Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln'sInn Fields, London WC2A 3PX, UK.
2 Bioinformatics and Biostatistics Service, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
3 Protein Analysis and Proteomics, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: frank.uhlmann{at}cancer.org.uk

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