Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54

Thomä, Nicolas H.; Czyzewski, Bryan K.; Alexeev, Andrei; Mazin, Alexander V.; Kowalczykowski, Stephen C.; Pavletich, Nikola P.

doi:10.1038/nsmb919

Cited by 174 publications

(205 citation statements)

References 48 publications

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“…Currently, there is no crystal structure of the ATPase domain of a nucleosome-binding remodeler (SWI/SNF or ISWI), but recent structures of the SWI/SNF-family member Rad54 (with DNA) show remarkable structural homology to the SF2 family of RNA and DNA translocases (see Fig. 3b) 5,60 . I will next summarize mechanistic insights from the translocase field and then apply those concepts to derive models for the movement of DNA on nucleosomes.…”

Section: Remodeler Atpases Resemble 'Dna Inchworms'mentioning

confidence: 99%

Chromatin remodeling: insights and intrigue from single-molecule studies

Cairns

2007

Nat Struct Mol Biol

227

208

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Chromatin remodelers are ATP-hydrolyzing machines specialized to restructure, mobilize or eject nucleosomes, allowing regulated exposure of DNA in chromatin. Recently, remodelers have been analyzed using single-molecule techniques in real time, revealing them to be complex DNA-pumping machines. The results both support and challenge aspects of current models of remodeling, supporting the idea that the remodeler translocates or pumps DNA loops into and around the nucleosome, while also challenging earlier concepts about loop formation, the character of the loop and how it propagates. Several complex behaviors were observed, such as reverse translocation and long translocation bursts of the remodeler, without appreciable DNA twist. This review presents and discusses revised models for nucleosome sliding and ejection that integrate this new information with the earlier biochemical studies.Many processes involving chromosomes are guided by DNA-binding proteins, and the access of these proteins to DNA is regulated by chromatin. Nucleosomes, the primary repeating unit of chromatin, package DNA by wrapping 147 base pairs (bp) around an octamer of histone proteins in ∼1.7 helical turns 1-3 . This packaging provides topological order but occludes one face of the DNA, which slows or prevents the recognition of DNA sequences by DNA-binding proteins. To maintain topological order, and also to allow rapid and regulated access to the DNA, cells have evolved a set of chromatin-remodeling machines that alter nucleosome position, presence and structure.Remodelers can be separated into several families on the basis of their composition and activities: SWI/SNF, ISWI, NURD/Mi-2/CHD and the 'split ATPases' INO80 and SWR1 (which bear an insertion within their ATPase domains). Rad54 may represent an additional family, as it perturbs chromatin in vitro, but it apparently lacks specific nucleosome-interacting domains 4,5 . The participation of remodelers in various chromosomal processes has been the subject of many reviews 6-9 . The present work focuses solely on remodeler mechanisms, and primarily on the function of their conserved catalytic subunit, a superfamily 2 (SF2) ATPdependent DNA translocase. Recently, single-molecule approaches have been used to examine several remodelers, providing many new insights into their behavior. Here I discuss these recent studies, compare them with previous biochemical studies and suggest refinements to existing models to account for some of the observations. Remodelers slide, eject and restructure nucleosomesRemodelers can affect nucleosomes in at least four ways ( Fig. 1): (i) sliding, or moving the histone octamer to a new position, which exposes DNA 10-12 ; (ii) ejection, or completely displacing the octamer to expose DNA [13][14][15][16] ; (iii) removal of H2A-H2B dimers, leaving only the central H3-H4 tetramer, which exposes DNA and destabilizes the nucleosome 17,18 ; and (iv) dimer replacement-for example, exchanging the resident H2A-H2B dimers for dimers NIH Public Access

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Section: Remodeler Atpases Resemble 'Dna Inchworms'mentioning

confidence: 99%

Chromatin remodeling: insights and intrigue from single-molecule studies

Cairns

2007

Nat Struct Mol Biol

227

208

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“…The ATPase domain consists of seven subdomains that structurally forms two lobes referred to as the DEXD and helicase motifs that form a cleft to which DNA binds based on X-ray crystal structure from the related Rad54 ATPase domain [41,42]. In addition the Swi2/Snf2 protein contains at its Cterminus a bromo domain which has been shown to recognize specific acetylated lysines in histone tails [43][44][45][46][47][48][49][50].…”

Section: Nucleosome Remodeling Complexes Swi/snf Familymentioning

confidence: 99%

Mechanisms of ATP dependent chromatin remodeling

Gangaraju

Bartholomew

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

128

159

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The inter-relationship between DNA repair and ATP dependent chromatin remodeling has begun to become very apparent with recent discoveries. ATP dependent remodeling complexes mobilize nucleosomes along DNA, promote the exchange of histones, or completely displace nucleosomes from DNA. These remodeling complexes are often categorized based on the domain organization of their catalytic subunit. The biochemical properties and structural information of several of these remodeling complexes are reviewed. The different models for how these complexes are able to mobilize nucleosomes and alter nucleosome structure are presented incorporating several recent findings. Finally the role of histone tails and their respective modifications in ATP-dependent remodeling are discussed.

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“…1a,d,e). In Rad54, the only Snf2 family ATPase that has been crystallized, this insertion consists of two protrusions (1 and 2) connected by a linker 29,30 (Fig. 1d).…”

Section: Sth1 and Mra Mutations Cluster Within Two Sth1 Domainsmentioning

confidence: 99%

The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases

Szerlong

Hinata

Viswanathan

et al. 2008

Nat Struct Mol Biol

189

246

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We identify the helicase-SANT-associated (HSA) domain as the primary binding platform for nuclear actin-related proteins (ARPs) and actin. Individual HSA domains from chromatin remodelers (RSC, yeast SWI-SNF, human SWI-SNF, SWR1 and INO80) or modifiers (NuA4) reconstitute their respective ARP-ARP or ARP-actin modules. In RSC, the HSA domain resides on the catalytic ATPase subunit Sth1. The Sth1 HSA is essential in vivo, and its omission causes the specific loss of ARPs and a moderate reduction in ATPase activity. Genetic selections for arp suppressors yielded specific gain-of-function mutations in two new domains in Sth1, the post-HSA domain and protrusion 1, which are essential for RSC function in vivo but not ARP association. Taken together, we define the role of the HSA domain and provide evidence for a regulatory relationship involving the ARP-HSA module and two new functional domains conserved in remodeler ATPases that contain ARPs.Transcriptional regulation involves the concerted action of chromatin regulators, transcription factors and the basal transcription machinery. The two general types of chromatin regulators are chromatin remodelers, which reposition and restructure nucleosomes 1 , and chromatin modifiers, which add or remove covalent marks from the histone proteins 2 . These chromatin regulatory complexes work together to mark and move nucleosomes, which can either help silence or activate transcription, depending on the context. Remodelers bear a catalytic ATPase subunit required for ATP-dependent nucleosome repositioning 1,3,4 , whereas modifier complexes bear one or more subunits with histone-modification potential 2,5,6 . However, in both cases, most of the subunits of chromatin regulatory complexes are nonenzymatic. These attendant subunits are specialized for diverse tasks: targeting the complex to particular nucleosomes, enabling complex association with particular DNA binding proteins or other complexes, or helping to regulate enzymatic activity.Intriguingly, actin and ARPs are among the associated subunits of certain chromatinremodeling and chromatin-modifying complexes 7-9 . ARPs have been studied extensively in the budding yeast Saccharomyces cerevisiae, which contains ten ARPs 10 . Four ARPs (ARPs

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Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54

Cited by 174 publications

References 48 publications

Chromatin remodeling: insights and intrigue from single-molecule studies

Chromatin remodeling: insights and intrigue from single-molecule studies

Mechanisms of ATP dependent chromatin remodeling

The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases

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