OVEREXPRESSION OF RAD51 PROTEIN STIMULATES HOMOLOGOUS RECOMBINATION AND INCREASES RESISTANCE OF MAMMALIAN-CELLS TO IONIZING-RADIATION

Rad51 proteins share both structural and functional homologies with th e bacterial recombinase RecA. The human Rad51 (HsRad51) is able to cat alyse strand exchange between homologous DNA molecules in vitro. Howev er the biological functions of Rad51 in mammals are largely unknown. I n order to address this question, we have cloned hamster Rad51 cDNA an d overexpressed the corresponding protein in CHO cells. We found that 2-3-fold overexpression of the protein stimulated the homologous recom bination between integrated genes by 20-fold indicating that Rad51 is a functional and key enzyme of an intrachromosomal recombination pathw ay. Cells overexpressing Rad51 were resistant to ionizing radiation wh en irradiated in late S/G(2) phase of the cell cycle. This suggests th at Rad51 participate in the repair of double-strand breaks most likely by homologous recombination involving sister chromatids formed after the S phase.