title: Regulation of the Rhp26ERCC6/CSB chromatin remodeler by a novel conserved leucine latch motif.
abstract: CSB/ERCC6 (Cockayne syndrome B protein/excision repair cross-complementation group 6), a member of a subfamily of SWI2/SNF2 (SWItch/sucrose nonfermentable)-related chromatin remodelers, plays crucial roles in gene expression and the maintenance of genome integrity. Here, we report the mechanism of the autoregulation of Rhp26, which is the homolog of CSB/ERCC6 in Schizosaccharomyces pombe. We identified a novel conserved protein motif, termed the "leucine latch," at the N terminus of Rhp26. The leucine latch motif mediates the autoinhibition of the ATPase and chromatin-remodeling activities of Rhp26 via its interaction with the core ATPase domain. Moreover, we found that the C terminus of the protein counteracts this autoinhibition and that both the N- and C-terminal regions of Rhp26 are needed for its proper function in DNA repair in vivo. The presence of the leucine latch motif in organisms ranging from yeast to humans suggests a conserved mechanism for the autoregulation of CSB/ERCC6 despite the otherwise highly divergent nature of the N- and C-terminal regions.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093;
authors.forename: Lanfeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Oliver
authors.initials: O
authors.lastname: Limbo
authors.affiliation: Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093;
authors.forename: Jia
authors.initials: J
authors.lastname: Fei
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110; Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, KS 66160; and.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109.
authors.forename: Bong
authors.initials: B
authors.lastname: Kim
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093;
authors.forename: Jenny
authors.initials: J
authors.lastname: Chong
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110; Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, KS 66160; and.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110; Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, KS 66160; and.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109.
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Ranish
authors.affiliation: Section of Molecular Biology, University of California, San Diego, La Jolla, CA 92093;
authors.forename: James T
authors.initials: JT
authors.lastname: Kadonaga
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093; dongwang@ucsd.edu.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D020816:Amino Acid Motifs; D002843:Chromatin / Q000201:enzymology* / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D029702:Schizosaccharomyces pombe Proteins; D004265:DNA Helicases
keywords: SNF2-like family ATPase; SWI2/SNF2; chromatin remodeling; enzyme autoregulation; flanking regions