ATP Hydrolysis Is Required for Relocating Cohesin from Sites Occupied by Its Scc2/4 Loading Complex

Hu, Bin; Itoh, Takehiko; Mishra, Ajay; Katoh, Yuki; Chan, Kok-Lung; Upcher, William R.; Godlee, Camilla; Roig, Maurici B.; Shirahige, Katsuhiko; Nasmyth, Kim

doi:10.1016/j.cub.2010.12.004

Cited by 177 publications

(249 citation statements)

References 44 publications

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“…In the absence of either loader complex subunit, cohesin rings assemble, but fail to be deposited (7,12,13). ATP hydrolysis by cohesin's structural maintenance of chromosome (SMC) subunits is required for cohesin loading, and deposition is inhibited when SMC hinge domains, which mediate Smc1/3 interactions within cohesin, are artificially tethered (8,14,15). Thus, Scc2/ Scc4 may activate cohesin's ATPase activity or facilitate a conformational change in cohesin structure that promotes its loading, perhaps by permitting transient hinge opening to allow chromatin to enter cohesin rings or by promoting cohesin oligomerization (14,16).…”

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confidence: 99%

Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity

Woodman

Fara

Dzieciątkowska

et al. 2014

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

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Sister chromatid cohesion (SCC), efficient DNA repair, and the regulation of some metazoan genes require the association of cohesins with chromosomes. Cohesins are deposited by a conserved heterodimeric loading complex composed of the Scc2 and Scc4 proteins in Saccharomyces cerevisiae, but how the Scc2/Scc4 deposition complex regulates the spatiotemporal association of cohesin with chromosomes is not understood. We examined Scc2 chromatin association during the cell division cycle and found that the affinity of Scc2 for chromatin increases biphasically during the cell cycle, increasing first transiently in late G 1 phase and then again later in G 2 /M. Inactivation of Scc2 following DNA replication reduces cellular viability, suggesting that this post S-phase increase in Scc2 chromatin binding affinity is biologically relevant. Interestingly, high and low Scc2 chromatin binding levels correlate strongly with the presence of full-length or amino-terminally cleaved forms of Scc2, respectively, and the appearance of the cleaved Scc2 species is promoted in vitro either by treatment with specific cell cycle-staged cellular extracts or by dephosphorylation. Importantly, Scc2 cleavage eliminates Scc2-Scc4 physical interactions, and an scc2 truncation mutant that mimics in vivo Scc2 cleavage is defective for cohesin deposition. These observations suggest a previously unidentified mechanism for the spatiotemporal regulation of cohesin association with chromosomes through cell cycle regulation of Scc2 cohesin deposition activity by Scc2 dephosphorylation and cleavage.M ultisubunit, ring-shaped cohesin complexes play key roles in chromosome morphogenesis that are required for faithful chromosome transmission to daughter cells. Newly replicated sister chromatids become tethered together by cohesins during S phase, which promotes chromosome biorientation on mitotic spindles (1). Cohesins also mediate efficient DNA double-strand break repair by homologous recombination (2, 3) and the formation or stabilization of chromatin loops that affect various nuclear processes, such as gene expression and Ig gene rearrangements (reviewed in refs. 4 and 5). Altered gene expression resulting from defective cohesinmediated chromatin looping is likely responsible for the pathogenesis of Cornelia de Lange Syndrome (CdLS), a dominantly inherited human developmental disorder (6).Sister chromatid cohesion (Scc) proteins form a heterodimeric cohesin deposition complex, but the complex's activity in deposition is not understood (7). Cohesins copurify with Scc2/Scc4, suggesting that Scc2/Scc4 plays a direct role in deposition (8-11). In the absence of either loader complex subunit, cohesin rings assemble, but fail to be deposited (7,12,13). ATP hydrolysis by cohesin's structural maintenance of chromosome (SMC) subunits is required for cohesin loading, and deposition is inhibited when SMC hinge domains, which mediate Smc1/3 interactions within cohesin, are artificially tethered (8,14,15). Thus, Scc2/ Scc4 may activate cohesin's ATPase activity or f...

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mentioning

confidence: 99%

Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity

Woodman

Fara

Dzieciątkowska

et al. 2014

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

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“…The molecules are thought to enter through a "gate" created by transient dissociation of the Smc-Smc hinge interface (9). This event, which leads to a potentially stable association with chromatin, depends on the activity of a separate complex called kollerin [composed of Sister chromatid cohesion protein 2 and 4 (Scc2/4)] (10, 11) as well as hydrolysis of ATP bound to both NBDs (12)(13)(14)(15).…”

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Pds5 promotes and protects cohesin acetylation

Chan

Gligoris

Upcher

et al. 2013

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

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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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“…In principle, this requires transient dissociation at one of three subunit interfaces: in between the Smc1-Smc3 hinges or at the interfaces between the SMC heads and the kleisin subunit (Smc3-Scc1 or Smc1-Scc1). As cohesin’s chromatin loading in vivo [34] and DNA entrapment in biochemical reconstitution systems [18] are ATP-dependent, opening of the DNA transport gate might be coupled with the actions of the SMC ATPase heads. In budding yeast, an Smc1 mutant protein that is defective in ATP binding (K39I, Walker A motif) failed to retain its stable interaction with Scc1 [35,36].…”

Section: Topological Dna Binding By Cohesinmentioning

confidence: 99%

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

Murayama

2018

Nucleus

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Cohesin is a ring-shaped, multi-subunit ATPase assembly that is fundamental to the spatiotemporal organization of chromosomes. The ring establishes a variety of chromosomal structures including sister chromatid cohesion and chromatin loops. At the core of the ring is a pair of highly conserved SMC (Structural Maintenance of Chromosomes) proteins, which are closed by the flexible kleisin subunit. In common with other essential SMC complexes including condensin and the SMC5-6 complex, cohesin encircles DNA inside its cavity, with the aid of HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A and TOR) repeat auxiliary proteins. Through this topological embrace, cohesin is thought to establish a series of intra- and interchromosomal interactions by tethering more than one DNA molecule. Recent progress in biochemical reconstitution of cohesin provides molecular insights into how this ring complex topologically binds and mediates DNA-DNA interactions. Here, I review these studies and discuss how cohesin mediates such chromosome interactions.

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ATP Hydrolysis Is Required for Relocating Cohesin from Sites Occupied by Its Scc2/4 Loading Complex

Cited by 177 publications

References 44 publications

Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity

Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity

Pds5 promotes and protects cohesin acetylation

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

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