title: The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Oncological Sciences, Huntsman Cancer Institute, 2000 Circle of Hope, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Szerlong
authors.forename: Kaede
authors.initials: K
authors.lastname: Hinata
authors.forename: Ramya
authors.initials: R
authors.lastname: Viswanathan
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Cairns
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D000199:Actins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases