Pds5 promotes and protects cohesin acetylation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 32; pp. 13020 - 13025
• Main Authors: Chan, Kok-Lung, Gligoris, Thomas, Upcher, William, Kato, Yuki, Shirahige, Katsuhiko, Nasmyth, Kim, Beckouët, Frédéric
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06.08.2013; National Acad Sciences
• Subjects: Acetylation; Acetyltransferases - genetics; Acetyltransferases - metabolism; Amino Acid Sequence; Binding Sites - genetics; Biological Sciences; Blotting, Western; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatids; Chromatin; Chromatin - genetics; Chromatin - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes, Fungal - genetics; Chromosomes, Fungal - metabolism; Cohesins; Cohesion; Deoxyribonucleic acid; DNA; DNA, Fungal - genetics; DNA, Fungal - metabolism; Fluorescence Recovery After Photobleaching; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Interphase; Life Sciences; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Mitosis; Molecular Sequence Data; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Protein Binding; Proteins; S Phase; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sequence Homology, Amino Acid; Yeasts; cell; gene
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1306900110

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.