Report

Sister chromatid cohesion establishment occurs in concert with lagging strand synthesis

Volume 11, Issue 11   June 1, 2012
Pages 2114 - 2121
http://dx.doi.org/10.4161/cc.20547
Keywords: CHL1 , CTF7/ECO1 , FEN1 , DNA replication, cohesion, establishment, replication fork
Authors: Soumya Rudra and Robert V. Skibbens

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Abstract:
Cohesion establishment is central to sister chromatid tethering reactions and requires Ctf7/Eco1-dependent acetylation of the cohesin subunit Smc3. Ctf7/Eco1 is essential during S phase, and a number of replication proteins (RFC complexes, PCNA and the DNA helicase Chl1) all play individual roles in sister chromatid cohesion. While the mechanism of cohesion establishment is largely unknown, a popular model is that Ctf7/Eco1 acetylates cohesins encountered by and located in front of the fork. In turn, acetylation is posited both to allow fork passage past cohesin barriers and convert cohesins to a state competent to capture subsequent production of sister chromatids. Here, we report evidence that challenges this pre-replicative cohesion establishment model. Our genetic and biochemical studies link Ctf7/Eco1 to the Okazaki fragment flap endonuclease, Fen1. We further report genetic and biochemical interactions between Fen1 and the cohesion-associated DNA helicase, Chl1. These results raise a new model wherein cohesin deposition and establishment occur in concert with lagging strand-processing events and in the presence of both sister chromatids.

Received: April 17, 2012; Accepted: April 28, 2012

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