title: Inactivation of RAD52 aggravates RAD54 defects in mice but not in Schizosaccharomyces pombe.
abstract: RAD52 and RAD54 genes from Saccharomyces cerevisiae are required for double-strand break repair through homologous recombination and show epistatic interactions i.e., single and double mutant strains are equally sensitive to DNA damaging agents. In here we combined mutations in RAD52 and RAD54 homologs in Schizosaccharomyces pombe and mice. The analysis of mutant strains in S. pombe demonstrated nearly identical sensitivities of rhp54, rad22A and rad22B double and triple mutants to X-rays, cis-diamminedichloroplatinum and hydroxyurea. In this respect, the fission yeast homologs of RAD54 and RAD52 closely resemble their counterparts in S. cerevisiae. To verify if inactivation of RAD52 affects the DNA damage sensitivities of RAD54 deficient mice, several endpoints were studied in double mutant mice and in bone marrow cells derived from these animals. Haemopoietic depression in bone marrow and the formation of micronuclei after in vivo exposure to mitomycine C (MMC) was not increased in either single or double mutant mice in comparison to wildtype animals. The induction of sister chromatid exchanges in splenocytes was slightly reduced in the RAD54 mutant. A similar reduction was detected in the double mutant. However, a deficiency of RAD52 exacerbates the MMC survival of RAD54 mutant mice and also has a distinct effect on the survival of bone marrow cells after exposure to ionizing radiation. These findings may be explained by additive defects in HR in the double mutant but may also indicate a more prominent role for single-strand annealing in the absence of Rad54.
authors: Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands.
authors: Femke A T
authors: FA
authors: de Vries
authors: José B M
authors: JB
authors: Zonneveld
authors: Annemarie
authors: A
authors: van Duijn-Goedhart
authors: Marianne
authors: M
authors: Roodbergen
authors: Jan
authors: J
authors: Boei
authors: Paul P W
authors: PP
authors: van Buul
authors: Jeroen
authors: J
authors: Essers
authors: Harry
authors: H
authors: van Steeg
authors: Albert A
authors: AA
authors: van Zeeland
authors: Jan
authors: J
authors: van Benthem
authors: Albert
authors: A
authors: Pastink
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004843:Epistasis, Genetic; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006410:Hematopoiesis / Q000235:genetics / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015162:Micronucleus Tests; D016685:Mitomycin / Q000633:toxicity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics
chemical_list: D000477:Alkylating Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C450139:Rad22B protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C085412:rad52 protein, S pombe; D016685:Mitomycin; D004265:DNA Helicases; C103534:Rad54l protein, mouse; C099034:Rhp54 protein, S pombe