Role of mammalian RAD51L2 (RAD51C) in recombination and genetic stability.
The highly conserved RAD51 protein has a central role in homologous recombination. Five novel RAD51-like genes have been identified in mammalian cells, but little is known about their functions. A DNA damage-sensitive hamster cell line, irs3, was found to have a mutation in the RAD51L2 gene and an undetectable level of RAD51L2 protein. Resistance of irs3 to DNA-damaging agents was significantly increased by expression of the human RAD51L2 gene, but not by other RAD51-like genes or RAD51 itself. Consistent with a role for RAD51L2 in homologous recombination, irs3 cells show a reduction in sister chromatid exchange, an increase in isochromatid breaks, and a decrease in damage-dependent RAD51 focus formation compared with wild type cells. As recently demonstrated for human cells, we show that RAD51L2 forms part of two separate complexes of hamster RAD51-like proteins. Strikingly, neither complex of RAD51-like proteins is formed in irs3 cells. Our results demonstrate that RAD51L2 has a key role in mammalian RAD51-dependent processes, contingent on the formation of protein complexes involved in homologous recombination repair.
French
Catherine A
CA
Medical Research Council, Radiation & Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, United Kingdom.
Masson
Jean-Yves
JY
Griffin
Carol S
CS
O'Regan
Paul
P
West
Stephen C
SC
Thacker
John
J
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005822:Genetic Vectors; D006801:Humans; D008856:Microscopy, Fluorescence; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D012854:Sister Chromatid Exchange; D014162:Transfection; D014965:X-Rays
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; C448305:RAD51C protein, human; D016685:Mitomycin