title: HOP2-MND1 modulates RAD51 binding to nucleotides and DNA.
abstract: The HOP2-MND1 heterodimer is required for progression of homologous recombination in eukaryotes. In vitro, HOP2-MND1 stimulates the DNA strand exchange activities of RAD51 and DMC1. We demonstrate that HOP2-MND1 induces changes in the conformation of RAD51 that profoundly alter the basic properties of RAD51. HOP2-MND1 enhances the interaction of RAD51 with nucleotide cofactors and modifies its DNA-binding specificity in a manner that stimulates DNA strand exchange. It enables RAD51 DNA strand exchange in the absence of divalent metal ions required for ATP binding and offsets the effect of the K133A mutation that disrupts ATP binding. During nucleoprotein formation HOP2-MND1 helps to load RAD51 on ssDNA restricting its dsDNA-binding and during the homology search it promotes dsDNA binding removing the inhibitory effect of ssDNA. The magnitude of the changes induced in RAD51 defines HOP2-MND1 as a 'molecular trigger' of RAD51 DNA strand exchange.
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102-1192, USA [2].
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Bugreev
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102-1192, USA [2].
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102-1192, USA.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Mazina
authors.affiliation: Oklahoma Medical Research Foundation, Department of Cell Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Pezza
authors.affiliation: Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Voloshin
authors.affiliation: Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102-1192, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Mazin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009711:Nucleotides / Q000378:metabolism*; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C501202:Hop2 protein, mouse; C501203:Mnd1 protein, mouse; D009711:Nucleotides; D000255:Adenosine Triphosphate; D004247:DNA; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse