title: ATP-dependent nucleosome unwrapping catalyzed by human RAD51.
abstract: Double-strand breaks (DSB) occur in chromatin following replication fork collapse and chemical or physical damage [Symington and Gautier (Double-strand break end resection and repair pathway choice. Annu. Rev. Genet. 2011;45:247-271.)] and may be repaired by homologous recombination (HR) and non-homologous end-joining. Nucleosomes are the fundamental units of chromatin and must be remodeled during DSB repair by HR [Andrews and Luger (Nucleosome structure(s) and stability: variations on a theme. Annu. Rev. Biophys. 2011;40:99-117.)]. Physical initiation of HR requires RAD51, which forms a nucleoprotein filament (NPF) that catalyzes homologous pairing and strand exchange (recombinase) between DNAs that ultimately bridges the DSB gap [San Filippo, Sung and Klein. (Mechanism of eukaryotic HR. Annu. Rev. Biochem. 2008;77:229-257.)]. RAD51 forms an NPF on single-stranded DNA and double-stranded DNA (dsDNA). Although the single-stranded DNA NPF is essential for recombinase initiation, the role of the dsDNA NPF is less clear. Here, we demonstrate that the human RAD51 (HsRAD51) dsDNA NPF disassembles nucleosomes by unwrapping the DNA from the core histones. HsRAD51 that has been constitutively or biochemically activated for recombinase functions displays significantly reduced nucleosome disassembly activity. These results suggest that HsRAD51 can perform ATP hydrolysis-dependent nucleosome disassembly in addition to its recombinase functions.
authors.affiliation: Department of Physics, The Ohio State University, Columbus OH 43210, USA, Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA, Chemistry and Biochemistry Department, The Ohio State University, Columbus OH 43210, USA and Human Cancer Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.forename: Ravindra
authors.initials: R
authors.lastname: Amunugama
authors.forename: Marcelina
authors.initials: M
authors.lastname: Klajner
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Bruns
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D015894:Genome, Human; D042822:Genomic Instability; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism; D059767:Recombinational DNA Repair; D018741:Replication Origin
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D002843:Chromatin; D004277:DNA, Single-Stranded; D006657:Histones; D009707:Nucleosomes; D000255:Adenosine Triphosphate; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D011938:Rec A Recombinases