Mammalian X ray sensitive mutants: a tool for the elucidation of the cellular response to ionizing radiation

The complexity of the cellular response to ionizing radiation is indicated by many complementation groups identified among mammalian cells sensitive to ionizing radiation. Genetic complementation analysis of these mutants has been based on cell fusion and complementation of cell killing by X ray, whereas complementation of RDS after gamma rays has led to false results among AT cell lines and could not also be used in rodent cells. Studies on the relationship between cell killing and RDS following gamma irradiation have indicated that (a) RDS is not responsible for cell killing and (b) DNA replication in response to gamma rays is controlled by several genes. Complementation groups established in rodent cell mutants have led to the identification of the gene function in several mutants, and remarkable progress has been made in the understanding of DSB repair and its involvement in V(D)J recombination. The remaining complementation groups of X ray sensitive mutants await the determination of the role of the defective genes in the pathways operating in mammalian cells against ionizing radiation. One group of rodent mutants seems to be defective in the gene homologous to the ATM gene, and so far no more human counterparts have been found among rodent mutants. Newly characterized mutants, V-C8 and UV40, showed combined features of several human disorders, suggesting that their defective gene products could be involved in several pathways handling the response to DNA damage.