c-abl tyrosine kinase is not essential for ataxia telangiectasia mutated functions in chromosomal maintenance

c-Abl is activated by DNA damage in an ataxia telangiectasia mutated (ATM)- dependent manner and plays important roles in growth arrest and apoptosis i nduced by DNA damage. c-Abl also interacts physically and functionally with Rad51, a key molecule in homologous recombinational (HR) DNA repair. To st udy further the roles of c-Abl in HR DNA repair, we generated c-Abl(-/-) an d ATM(-/-)/c-Abl(-/-) mutant cell lines from a chicken B lymphocyte DT40 ce ll line, comparing the phenotypes of these mutants to those of ATM(-/-) DT4 0 cells that we had created previously. We found that the time course of ra diation-induced Rad51 focus formation is abnormal in ATM(-/-) DT40 cells, c onsistent with the observation that ATM(-/-) DT40 cells display hypersensit ivity to ionizing radiation and highly elevated frequencies of both spontan eous and radiation-induced chromosomal aberrations. In contrast, c-Abl(-/-) cells did not show these ATM-related defects in their cellular response to radiation, nor did the disruption of c-Abl in ATM(-/-) DT40 cells exacerba te these ATM-related defects. However, c-Abl(-/-) DT40 cells, but not ATM(- /-) DT40 cells, were resistant to radiation-induced apoptosis, indicating a n important role for c-Abl in this cellular response to ionizing radiation. These results therefore indicate that, although ATM plays an important rol e in genome maintenance, c-Abl is not essential for this ATM function. Thes e findings suggest that c-Abl and ATM play important roles in the maintenan ce of the cell homeostasis in response to DNA damage that are, at least in part, independent.