Conserved roles of chromatin remodellers in cohesin loading onto chromatin
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ORIGINAL ARTICLE
Conserved roles of chromatin remodellers in cohesin loading onto chromatin Sofía Muñoz1 · Francesca Passarelli1 · Frank Uhlmann1 Received: 20 March 2020 / Revised: 28 March 2020 / Accepted: 31 March 2020 © The Author(s) 2020
Abstract Cohesin is a conserved, ring-shaped protein complex that topologically entraps DNA. This ability makes this member of the structural maintenance of chromosomes (SMC) complex family a central hub of chromosome dynamics regulation. Besides its essential role in sister chromatid cohesion, cohesin shapes the interphase chromatin domain architecture and plays important roles in transcriptional regulation and DNA repair. Cohesin is loaded onto chromosomes at centromeres, at the promoters of highly expressed genes, as well as at DNA replication forks and sites of DNA damage. However, the features that determine these binding sites are still incompletely understood. We recently described a role of the budding yeast RSC chromatin remodeler in cohesin loading onto chromosomes. RSC has a dual function, both as a physical chromatin receptor of the Scc2/Scc4 cohesin loader complex, as well as by providing a nucleosome-free template for cohesin loading. Here, we show that the role of RSC in sister chromatid cohesion is conserved in fission yeast. We discuss what is known about the broader conservation of the contribution of chromatin remodelers to cohesin loading onto chromatin. Keywords Cohesin · Chromatin remodellers · RSC · Scc2–Scc4 · Cornelia de lange syndrome · Coffin–Siris syndrome
Introduction Cohesin is a central regulator of chromosome architecture, performing prominent roles in sister chromatid cohesion, genome organization, transcriptional regulation and DNA repair. This is accomplished due to its ability of trapping one or more molecules of DNA inside its ring-shaped structure (Litwin and Wysocki 2018; Nasmyth and Haering 2009; Peters and Nishiyama 2012; Villa-Hernandez and Bermejo 2018). Cohesin loading onto chromosomes requires a specialised cohesin loader complex, comprised of the Scc2 and Scc4 subunits (Ciosk et al. 2000; Gillespie and Hirano 2004). In vitro, Scc2–Scc4 loads cohesin in a DNA sequence independent manner (Murayama and Uhlmann 2014), whereas in vivo, cohesin is loaded at specific Communicated by M. Kupiec. * Sofía Muñoz sofia.munoz‑[email protected] * Frank Uhlmann [email protected] 1
Chromosome Segregation Laboratory, The Francis Crick Institute, London, UK
chromosomal locations. The chromosomal loading sites of the cohesin complex at centromeres and promoters of certain highly transcribed genes have been known for some time (Kagey et al. 2010; Lopez-Serra et al. 2014; Petela et al. 2018; Zuin et al. 2014). However, the features that define these cohesin loading sites are incompletely understood. In the budding yeast Saccharomyces cerevisiae, the ‘Remodels the Structure of Chromatin’ (RSC) chromatinremodelling complex co-occupies the genomic cohesin loader locations and is necessary for the cohesin loader recruitment to those sites (L
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