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Cohesin's Smc1 and Smc3 subunits form V-shaped heterodimers, the nucleotide binding domains (NBDs) of which bind the C- and N-terminal domains, respectively, of the α-kleisin subunit, forming a large tripartite ring within in which sister DNAs are entrapped, and thereby held together (sister chromatid cohesion). During replication, establishment of stable cohesion is dependent on Eco1-mediated acetylation of Smc3's NBD, which is thought to prevent dissociation of α-kleisin from Smc3, thereby locking shut a "DNA exit gate." How Scc3 and Pds5, regulatory subunits bound to α-kleisin, regulate cohesion establishment and maintenance is poorly understood. We show here that by binding to α-kleisin adjacent to its Smc3 nucleotide binding N-terminal domain, Pds5 not only promotes cohesin's release from chromatin but also mediates de novo acetylation of Smc3 by Eco1 during S phase and subsequently prevents de-acetylation by the deacetylase Hos1/HDAC8. By first promoting cohesin's release from chromosomes and subsequently creating and guarding the chemical modification responsible for blocking release, Pds5 enables chromosomal cohesin to switch during S phase from a state of high turnover to one capable of tenaciously holding sister chromatids together for extended periods of time, a duality that has hitherto complicated analysis of this versatile cohesin subunit.

Original publication

DOI

10.1073/pnas.1306900110

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

06/08/2013

Volume

110

Pages

13020 - 13025

Keywords

cell, gene, Acetylation, Acetyltransferases, Amino Acid Sequence, Binding Sites, Blotting, Western, Cell Cycle Proteins, Chromatin, Chromosomal Proteins, Non-Histone, Chromosomes, Fungal, DNA, Fungal, Fluorescence Recovery After Photobleaching, Histone Deacetylases, Luminescent Proteins, Molecular Sequence Data, Mutation, Nuclear Proteins, Protein Binding, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid