title: Homologous recombination in budding yeast expressing the human RAD52 gene reveals a Rad51-independent mechanism of conservative double-strand break repair.
abstract: RAD52 is a homologous recombination (HR) protein that is conserved from bacteriophage to humans. Simultaneously attenuating expression of both the RAD52 gene, and the HR and tumor suppressor gene, BRCA2, in human cells synergistically reduces HR - indicating that RAD52 and BRCA2 control independent mechanisms of HR. We have expressed the human RAD52 gene (HsRAD52) in budding yeast strains lacking the endogenous RAD52 gene and found that HsRAD52 supports repair of DNA double-strand breaks (DSB) by a mechanism of HR that conserves genome structure. Importantly, this mechanism of HR is independent of RAD51, which encodes the central strand exchange protein in yeast required for conservative HR. In contrast, BRCA2 exerts its effect on HR in human cells together with HsRAD51, potentially explaining the synergistic effect of attenuating the expression of both HsRAD52 and BRCA2. This suggests that multiple mechanisms of conservative DSB repair may contribute to tumor suppression in human cells.
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Manthey
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.|Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Alissa D
authors.initials: AD
authors.lastname: Clear
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Liddell
authors.affiliation: Department of Biology, Pomona College, Claremont, CA 91711, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Negritto
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.|Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Bailis
mesh_terms: D047369:Chromatin Immunoprecipitation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D000066630:Ectopic Gene Expression; D059765:Homologous Recombination; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051135:Rad51 Recombinase / Q000378:metabolism*; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics* / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D004718:Saccharomycetales / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D020798:Two-Hybrid System Techniques
chemical_list: C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D051135:Rad51 Recombinase