Targeted Inactivation of Mouse RAD52 Reduces Homologous Recombination but Not Resistance to Ionizing Radiation |
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| Authors: | Tonnie Rijkers Jody Van Den Ouweland Bruno Morolli Anton G. Rolink Willy M. Baarends Petra P. H. Van Sloun Paul H. M. Lohman Albert Pastink |
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| Affiliation: | MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Leiden,1. and Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam,3. The Netherlands, and Basel Institute for Immunology, Basel, Switzerland2. |
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| Abstract: | 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. |
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