Sororin Is Required for Stable Binding of Cohesin to Chromatin and for Sister Chromatid Cohesion in Interphase

Schmitz, Julia; Watrin, Erwan; Lénárt, Péter; Mechtler, Karl; Peters, Jan‐Michael

doi:10.1016/j.cub.2007.02.029

Cited by 213 publications

(284 citation statements)

References 26 publications

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“…Depletion of Wapl, a protein that co-immunoprecipitates with the cohesin complex, by RNAi in HeLa cells results in an increase in the residence time of the 'fast' population of Scc1 (Kueng et al 2006). In contrast, depletion of sororin reduces the amount of Smc1 that is stably bound to chromatin (Schmitz et al 2007). Mutations in Scc2/Nipped-B result in the localized loss of cohesin and cohesin-mediated enhancer blocking at the cut gene locus in Drosophila (Rollins et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

McNairn

Gerton

2009

Chromosome Res

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The evolutionarily conserved cohesin proteins Smc1, Smc3, Rad21 (Mcd1), and Scc3 function in the cohesin complex that provides the basis for chromosome cohesion and is involved in gene regulation. Understanding how these proteins link together the genome requires the use of wholegenome approaches to study the molecular mechanisms of these essential proteins. While chromatin immunoprecipitation followed by DNA microarray (ChIP-chip) studies have provided a snapshot in time of where these proteins associate with various genomes, the cohesin proteins are dynamic in their localization and interactions on chromatin. Study of the dynamic nature of these proteins requires approaches such as live cell imaging. We present evidence from fluorescence loss in photobleaching (FLIP) experiments in budding yeast that the decay constant of each cohesin subunit is ∼60-90 s in interphase. The decay constant on chromatin increases from G 1 to S phase to metaphase, consistent with the interaction with chromatin becoming more stable once chromosomes are cohered. A small population of Smc3 at a position consistent with centromeric location has a longer decay constant than bulk Smc3. The characterization of the interaction of cohesin with chromatin, in terms of both its position and its dynamics, may be key to understanding how this protein complex contributes to chromosome segregation and gene regulation.

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Section: Discussionmentioning

confidence: 99%

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

McNairn

Gerton

2009

Chromosome Res

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“…ABC-like nucleotide binding domains (NBDs) at the vertices of Smc dimers are bound by C-and N-terminal domains of α-kleisin subunits, respectively, thereby creating huge tripartite rings within which sister DNAs are thought be entrapped (1,2). The ability of these rings to build, maintain, and dissolve cohesion depends on their association with a number of regulatory subunits, including Scc3, Pds5, Sororin, and Wapl (3)(4)(5)(6)(7)(8).…”

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confidence: 99%

Pds5 promotes and protects cohesin acetylation

Chan

Gligoris

Upcher

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

116

161

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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.cell | gene

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“…During DNA replication in S phase, the ATPase head domain of Smc3 is acetylated by the acetyltransferase establishment of cohesion protein 1 (Eco1) (8)(9)(10)(11)(12)(13). In vertebrates, replication-coupled Smc3 acetylation enables the binding of precocious dissociation of sisters protein 5 (Pds5) and sororin to cohesin (14)(15)(16)(17). Sororin counteracts Wapl to stabilize cohesin on replicated chromatin and establishes sister-chromatid cohesion (15).…”

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confidence: 99%

Structure of the human cohesin inhibitor Wapl

Ouyang

Song

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Cohesin, along with positive regulators, establishes sister-chromatid cohesion by forming a ring to circle chromatin. The wings apart-like protein (Wapl) is a key negative regulator of cohesin and forms a complex with precocious dissociation of sisters protein 5 (Pds5) to promote cohesin release from chromatin. Here we report the crystal structure and functional characterization of human Wapl. Wapl contains a flexible, variable N-terminal region (Wapl-N) and a conserved C-terminal domain (Wapl-C) consisting of eight HEAT (Huntingtin, Elongation factor 3, A subunit, and target of rapamycin) repeats. Wapl-C folds into an elongated structure with two lobes. Structure-based mutagenesis maps the functional surface of Wapl-C to two distinct patches (I and II) on the N lobe and a localized patch (III) on the C lobe. Mutating critical patch I residues weaken Wapl binding to cohesin and diminish sister-chromatid resolution and cohesin release from mitotic chromosomes in human cells and Xenopus egg extracts. Surprisingly, patch III on the C lobe does not contribute to Wapl binding to cohesin or its known regulators. Although patch I mutations reduce Wapl binding to intact cohesin, they do not affect Wapl-Pds5 binding to the cohesin subcomplex of sister chromatid cohesion protein 1 (Scc1) and stromal antigen 2 (SA2) in vitro, which is instead mediated by Wapl-N. Thus, Wapl-N forms extensive interactions with Pds5 and Scc1-SA2. Wapl-C interacts with other cohesin subunits and possibly unknown effectors to trigger cohesin release from chromatin.chromosome segregation | crystallography | genomic stability | mitosis | protein-protein interaction P roper chromosome segregation during mitosis maintains genomic stability. Errors in this process cause aneuploidy, which contributes to tumorigenesis under certain contexts (1). Timely establishment and dissolution of sister-chromatid cohesion are critical for accurate chromosome segregation and require the cell-cycle-regulated interactions between cohesin and its regulators (2-4).In human cells, cohesin consists of four core subunits: Structural maintenance of chromosomes 1 (Smc1), Smc3, sister chromatid cohesion protein 1 (Scc1), and stromal antigen 1 or 2 (SA1/2). Smc1 and Smc3 are related ATPases, and each contains an ATPase head domain, a long coiled-coil domain, and a hinge domain that mediates Smc1-Smc3 heterodimerization. The Smc1-Smc3 heterodimer associates with the Scc1-SA1/2 heterodimer to produce the intact cohesin. Specifically, the N-and C-terminal winged helix domains (WHDs) of Scc1 connect the ATPase domains of Smc3 and Smc1, respectively, forming a ring (4).Cohesin is loaded onto chromatin in telophase/G1, but the chromatin-bound cohesin at this stage is highly dynamic and is actively removed from chromatin by the cohesin inhibitor Wings apart-like protein (Wapl) (5-7). During DNA replication in S phase, the ATPase head domain of Smc3 is acetylated by the acetyltransferase establishment of cohesion protein 1 (Eco1) (8-13). In vertebrates, replication-coupled Smc3 acet...

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Sororin Is Required for Stable Binding of Cohesin to Chromatin and for Sister Chromatid Cohesion in Interphase

Cited by 213 publications

References 26 publications

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins

Pds5 promotes and protects cohesin acetylation

Structure of the human cohesin inhibitor Wapl

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