Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination.
Double-strand DNA break (DSB) repair by homologous recombination occurs through the RAD52 pathway in Saccharomyces cerevisiae. Its biological importance is underscored by the conservation of many RAD52 pathway genes, including RAD54, from fungi to humans. We have analyzed the phenotype of mouse RAD54-/- (mRAD54-/-) cells. Consistent with a DSB repair defect, these cells are sensitive to ionizing radiation, mitomycin C, and methyl methanesulfonate, but not to ultraviolet light. Gene targeting experiments demonstrate that homologous recombination in mRAD54-/- cells is reduced compared to wild-type cells. These results imply that, besides DNA end-joining mediated by DNA-dependent protein kinase, homologous recombination contributes to the repair of DSBs in mammalian cells. Furthermore, we show that mRAD54-/- mice are viable and exhibit apparently normal V(D)J and immunoglobulin class-switch recombination. Thus, mRAD54 is not required for the recombination processes that generate functional immunoglobulin and T cell receptor genes.
Essers
J
J
Medical Genetics Center, Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.
Hendriks
R W
RW
Swagemakers
S M
SM
Troelstra
C
C
de Wit
J
J
Bootsma
D
D
Hoeijmakers
J H
JH
Kanaar
R
R
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004274:DNA, Recombinant; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005720:Gamma Rays; D018390:Gene Targeting; D005803:Genes, Immunoglobulin / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D016685:Mitomycin / Q000494:pharmacology; D010641:Phenotype; D011836:Radiation Tolerance; D011995:Recombination, Genetic / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D000477:Alkylating Agents; D004274:DNA, Recombinant; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D016685:Mitomycin; D008741:Methyl Methanesulfonate; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes