Targeted inactivation of mouse RAD52 reduces homologous recombination but not resistance to ionizing radiation.
The RAD52 epistasis group is required for recombinational repair of double-strand breaks (DSBs) and shows strong evolutionary conservation. In Saccharomyces cerevisiae, RAD52 is one of the key members in this pathway. Strains with mutations in this gene show strong hypersensitivity to DNA-damaging agents and defects in recombination. Inactivation of the mouse homologue of RAD52 in embryonic stem (ES) cells resulted in a reduced frequency of homologous recombination. Unlike the yeast Scrad52 mutant, MmRAD52(-/-) ES cells were not hypersensitive to agents that induce DSBs. MmRAD52 null mutant mice showed no abnormalities in viability, fertility, and the immune system. These results show that, as in S. cerevisiae, MmRAD52 is involved in recombination, although the repair of DNA damage is not affected upon inactivation, indicating that MmRAD52 may be involved in certain types of DSB repair processes and not in others. The effect of inactivating MmRAD52 suggests the presence of genes functionally related to MmRAD52, which can partly compensate for the absence of MmRad52 protein.
MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Leiden, The Netherlands.
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T
Rijkers
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J
Van Den Ouweland
B
B
Morolli
A G
AG
Rolink
W M
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Baarends
P P
PP
Van Sloun
P H
PH
Lohman
A
A
Pastink
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005434:Flow Cytometry; D007134:Immunoglobulin Switch Region / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051721:Rad52 DNA Repair and Recombination Protein; D011839:Radiation, Ionizing; D011995:Recombination, Genetic / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014965:X-Rays
D004268:DNA-Binding Proteins; D051721:Rad52 DNA Repair and Recombination Protein; C497196:Rad52 protein, mouse