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.
Highlights
Cohesin is a central regulator of chromosome architecture, performing prominent roles in sister chromatid cohesion, genome organization, transcriptional regulation and DNA repair
Cornelia de Lange Syndrome (CdLS) shows overlapping clinical features with Coffin–Siris syndrome (Fryns 1986), which is caused by mutations in various subunits of the human switch/sucrose non-fermentable (SWI/SNF) chromatin-remodelling complexes (Santen et al 2012; Tsurusaki et al 2014) suggesting the existence of a functional link between the human cohesin loader and RSC orthologs with important clinical implications
imitation switch (ISWI), has been implicated in cohesin loading onto chromosomes in human cells (Hakimi et al 2002), opening the possibility that additional or different chromatin remodeller classes contribute as chromatin receptors during cohesin loading
Summary
Cohesin is a central regulator of chromosome architecture, performing prominent roles in sister chromatid cohesion, genome organization, transcriptional regulation and DNA repair. CdLS shows overlapping clinical features with Coffin–Siris syndrome (Fryns 1986), which is caused by mutations in various subunits of the human SWI/SNF chromatin-remodelling complexes (Santen et al 2012; Tsurusaki et al 2014) suggesting the existence of a functional link between the human cohesin loader and RSC orthologs with important clinical implications Another chromatin remodeller family, ISWI (imitation switch), has been implicated in cohesin loading onto chromosomes in human cells (Hakimi et al 2002), opening the possibility that additional or different chromatin remodeller classes contribute as chromatin receptors during cohesin loading. To assess the contribution of chromatin remodellers to sister chromatid cohesion in fission yeast, we individually deleted non-essential catalytical subunits of S. pombe chromatin remodellers We did this in a strain background harbouring an array of Lac operators next to the centromere of chromosome II and expressing a GFP-LacI repressor fusion protein to visualize this locus (Garcia et al 2002). Co-precipitation of Ssl, fused to a Pk epitope tag, was analyzed by immunoblotting
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