Targeted Inactivation of Mouse RAD52Reduces Homologous Recombination but Not Resistance to Ionizing Radiation

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 RAD52in 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, MmRAD52is 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.

ACKNOWLEDGMENTS

This work was supported by grants from the Dutch Cancer Society (EUR 94-858) and Euratom (F14 PCT950010). The Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche & Co.

We are grateful to M. Gassmann, H. te Riele, R. Kanaar, J. Essers, and E. Robanus-Maandag for the generous gift of cells and reagents. We thank J. Eeken, J. Jansen, and M. Zdzienicka for comments on the manuscript.