title: hXRCC2 enhances ADP/ATP processing and strand exchange by hRAD51.
abstract: The assembly of bacterial RecA, and its human homolog hRAD51, into an operational ADP/ATP-regulated DNA-protein (nucleoprotein) filament is essential for homologous recombination repair (HRR). Yet hRAD51 lacks the coordinated ADP/ATP processing exhibited by RecA and is less efficient in HRR reactions in vitro. In this study, we demonstrate that hXRCC2, one of five other poorly understood non-redundant human mitotic RecA homologs (hRAD51B, hRAD51C, hRAD51D, hXRCC2, and hXRCC3), stimulates hRAD51 ATP processing. hXRCC2 also increases hRAD51-mediated DNA unwinding and strand exchange activities that are integral for HRR. Although there does not seem to be a long-lived interaction between hXRCC2 and hRAD51, we detail a strong adenosine nucleotide-regulated interaction between the hXRCC2-hRAD51D heterodimer and hRAD51. These observations begin to elucidate the separate and specialized functions of the human mitotic RecA homologs that enable an efficient nucleoprotein filament required for HRR.
authors.affiliation: Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Kang Sup
authors.initials: KS
authors.lastname: Shim
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmutte
authors.forename: Gregory
authors.initials: G
authors.lastname: Tombline
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Heinen
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001665:Binding Sites; D015374:Biosensing Techniques; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008938:Mitosis; D011233:Precipitin Tests; D011485:Protein Binding; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; C113187:XRCC2 protein, human; C022571:adenosine 5'-O-(3-thiotriphosphate); D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004247:DNA; D005982:Glutathione Transferase; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases