Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

Fernius, Josefin; Nerusheva, Olga O.; Galander, Stefan; Alves, Flávia de Lima; Rappsilber, Juri; Marston, Adèle L.

doi:10.1016/j.cub.2013.02.022

Cited by 76 publications

(97 citation statements)

References 30 publications

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“…Further experimentation will be required, however, to determine whether Scc2 is a direct substrate of Cdc14 in vitro. Furthermore, our finding that Scc2 remains chromatin associated until early telophase contradicts a recent suggestion that Scc2/Scc4 chromatin association is cohesin dependent, because cohesins are removed from chromosomes at the metaphase/anaphase transition by separasedependent proteolysis (44,45).…”

Section: Discussioncontrasting

confidence: 57%

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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Section: Discussioncontrasting

confidence: 57%

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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“…Consistent with this, cohesin is highly enriched in a 50-kb domain around yeast centromeres, presumably to resist the pulling forces of microtubules (Megee et al 1999;Tanaka et al 1999;Glynn et al 2004). The kinetochore is required to recruit pericentromeric cohesin, and the COMA subcomplex has been specifically implicated in this process (Tanaka et al 1999;Weber et al 2004;Eckert et al 2007;Fernius and Marston 2009;Ng et al 2009;Fernius et al 2013). However, the details of how cohesin spreads from kinetochores to a large domain around the centromere are still unknown.…”

Section: Kinetochore Biorientationmentioning

confidence: 99%

“…These properties are regulated by the Bub1 and Sgo1 proteins as well as various chromatin-remodeling complexes (Haase et al 2012;Verdaasdonk et al 2012). While heterochromatin recruits pericentric cohesin in some organisms (Bernard et al 2001;Fukagawa et al 2004), components of the kinetochore itself direct cohesion enrichment in budding yeast (Megee et al 1999;Tanaka et al 1999;Weber et al 2004;Eckert et al 2007;Fernius and Marston 2009;Ng et al 2009;Fernius et al 2013).…”

Section: The Centromerementioning

confidence: 99%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule-kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed. TABLE OF CONTENTS Abstract 817Introduction 818

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“…Saccharomyces cerevisiae, Saccharomyces pombe, Homo sapiens, Xenopus, Drosophila melanogaster and Coprinopsis cinerea, the cohesin ring is loaded on chromatin by the Scc2-Scc4 complex (Fernius et al, 2013;Dorsett, 2004). Arabidopsis cohesin loading complex subunit AtSCC2 has been reported to control localization of cohesin during meiotic cell division, which was demonstrated using immunostaining of fixed plant material (Sebastian et al, 2009).…”

Section: In Vivo Imaging Of Cohesin Loadingmentioning

confidence: 99%

The Arabidopsis homolog of Scc4/MAU2 is essential for embryogenesis

Minina¹,

Reza²,

Gutiérrez-Beltrán³

et al. 2017

Development

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Factors regulating dynamics of chromatin structure have direct impact on expression of genetic information. Cohesin is a multi-subunit protein complex that is crucial for pairing sister chromatids during cell division, DNA repair and regulation of gene transcription and silencing. In non-plant species, cohesin is loaded on chromatin by the Scc2-Scc4 complex (also known as the NIBPL-MAU2 complex). Here, we identify the Arabidopsis homolog of Scc4, which we denote Arabidopsis thaliana (At)SCC4, and show that it forms a functional complex with AtSCC2, the homolog of Scc2. We demonstrate that AtSCC2 and AtSCC4 act in the same pathway, and that both proteins are indispensable for cell fate determination during early stages of embryo development. Mutant embryos lacking either of these proteins develop only up to the globular stage, and show the suspensor overproliferation phenotype preceded by ectopic auxin maxima distribution. We further establish a new assay to reveal the AtSCC4-dependent dynamics of cohesin loading on chromatin in vivo. Our findings define the Scc2-Scc4 complex as an evolutionary conserved machinery controlling cohesin loading and chromatin structure maintenance, and provide new insight into the plant-specific role of this complex in controlling cell fate during embryogenesis.

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Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

Cited by 76 publications

References 30 publications

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

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

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

The Arabidopsis homolog of Scc4/MAU2 is essential for embryogenesis

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