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Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1.

ABSTRACT: Sister chromatid cohesion is mediated by cohesin, whose Smc1, Smc3, and kleisin (Scc1) subunits form a ring structure that entraps sister DNAs. The ring is opened either by separase, which cleaves Scc1 during anaphase, or by a releasing activity involving Wapl, Scc3, and Pds5, which bind to Scc1 and open its interface with Smc3. We present crystal structures of Pds5 from the yeast L. thermotolerans in the presence and absence of the conserved Scc1 region that interacts with Pds5. Scc1 binds along the spine of the Pds5 HEAT repeat fold and is wedged between the spine and C-terminal hook of Pds5. We have isolated mutants that confirm the observed binding mode of Scc1 and verified their effect on cohesin by immunoprecipitation and calibrated ChIP-seq. The Pds5 structure also reveals architectural similarities to Scc3, the other large HEAT repeat protein of cohesin and, most likely, Scc2.

SUBMITTER: Lee BG

PROVIDER: S-EPMC4793087 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Crystal Structure of the Cohesin Gatekeeper Pds5 and in Complex with Kleisin Scc1.

Lee Byung-Gil BG Roig Maurici B MB Jansma Marijke M Petela Naomi N Metson Jean J Nasmyth Kim K Löwe Jan J

Cell reports 20160225 9

Sister chromatid cohesion is mediated by cohesin, whose Smc1, Smc3, and kleisin (Scc1) subunits form a ring structure that entraps sister DNAs. The ring is opened either by separase, which cleaves Scc1 during anaphase, or by a releasing activity involving Wapl, Scc3, and Pds5, which bind to Scc1 and open its interface with Smc3. We present crystal structures of Pds5 from the yeast L. thermotolerans in the presence and absence of the conserved Scc1 region that interacts with Pds5. Scc1 binds alon ...[more]

PMID: 26923598

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:The fission yeast Schizosaccharomyces pombe is a powerful genetic model system for uncovering fundamental principles of heterochromatin assembly and epigenetic inheritance of chromatin states. Heterochromatin defined by histone H3 lysine 9 methylation and HP1 proteins coats large chromosomal domains at centromeres, telomeres, and the mating-type (mat) locus. Although genetic and biochemical studies have provided valuable insights into heterochromatin assembly, many key mechanistic details remain unclear. Here, we use a sensitized reporter system at the mat locus to screen for factors affecting heterochromatic silencing. In addition to known components of heterochromatin assembly pathways, our screen identified eight new factors including the cohesin-associated protein Pds5. We find that Pds5 enriched throughout heterochromatin domains is required for proper maintenance of heterochromatin. This function of Pds5 requires its associated Eso1 acetyltransferase, which is implicated in the acetylation of cohesin. Indeed, introducing an acetylation-mimicking mutation in a cohesin subunit suppresses defects in heterochromatin assembly in pds5? and eso1? cells. Our results show that in cells lacking Pds5, cohesin interferes with heterochromatin assembly. Supporting this, eliminating cohesin from the mat locus in the pds5? mutant restores both heterochromatin assembly and gene silencing. These analyses highlight an unexpected requirement for Pds5 in ensuring proper coordination between cohesin and heterochromatin factors to effectively maintain gene silencing.

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