Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death

Yeast rad51 mutants are viable, but extremely sensitive to gamma-rays due to defective repair of double-strand breaks, In contrast, disruption of the murine RAD51 homologue is lethal, indicating an essential role of Rad51 in vertebrate cells. We generated clones of the chicken B lymphocyte line DT40 carrying a human RAD51 transgene under the control of a repressible promoter and subsequently disrupted the endogenous RAD51 loci, Upon inhibition of the RAD51 transgene, Rad51(-) cells accumulated in the G(2)/M phase of the cell cycle before dying. Chromosome analysis revealed that most metaphase-arrested Rad51(-) cells carried isochromatid-type breaks, In conclusion, Rad51 fulfils an essential role in the repair of spontaneously occurring chromosome breaks in proliferating cells of higher eukaryotes.