title: Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells.
abstract: Yeast Rad52 DNA-repair mutants exhibit pronounced radiation sensitivity and a defect in homologous re combination (HR), whereas vertebrate cells lacking Rad52 exhibit a nearly normal phenotype. Bio chemical studies show that both yeast Rad52 and Rad55-57 (Rad51 paralogs) stimulate DNA-strand exchange mediated by Rad51. These findings raise the possibility that Rad51 paralogs may compensate for lack of Rad52 in vertebrate cells, explaining the absence of prominent phenotypes for Rad52-deficient cells. To test this hypothesis, using chicken DT40 cells, we generated conditional mutants deficient in both RAD52 and XRCC3, which is one of the five vertebrate RAD51 paralogs. Surprisingly, the rad52 xrcc3 double-mutant cells were non-viable and exhibited extensive chromosomal breaks, whereas rad52 and xrcc3 single mutants grew well. Our data reveal an overlapping (but non-reciprocal) role for Rad52 and XRCC3 in repairing DNA double-strand breaks. The present study shows that Rad52 can play an important role in HR repair by partially substituting for a Rad51 paralog.
authors.affiliation: Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fujimori
authors.forename: S
authors.initials: S
authors.lastname: Tachiiri
authors.forename: E
authors.initials: E
authors.lastname: Sonoda
authors.forename: L H
authors.initials: LH
authors.lastname: Thompson
authors.forename: P K
authors.initials: PK
authors.lastname: Dhar
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Reth
authors.forename: M
authors.initials: M
authors.lastname: Takata
mesh_terms: D000818:Animals; D030161:Avian Proteins; D005075:Biological Evolution; D002875:Chromosomes / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005804:Genes, Lethal; D006801:Humans; D051135:Rad51 Recombinase; D011995:Recombination, Genetic
chemical_list: D030161:Avian Proteins; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C495150:RAD51 protein, Gallus gallus; C495153:RAD51 protein, human; D051135:Rad51 Recombinase