Abstract
The abnormal radiosensitivity of Ataxia Telangiectasia cells is ascribed to the results of defective double-strand DNA breaks (DNAdsb) repair or enhanced misrepair. DNAdsb are repaired by homologous recombination, Ku-mediated nonhomologous end joining and 53BP1-mediated nonhomologous end joining. Although ATM is considered to contribute to homologous recombination, there are controversial reports on ATM involvement in nonhomologous end joining and also that ATM does not contribute to homologous recombination of I-SceI induced DNAdsb. Thus, ATM association with DNA repair pathways still remains unclear. In this study, we examined ATM relation to three pathways using a selective ATM inhibitor and RNAi knockdown of 53BP1 in Ku70 defective cells.
The increased radiosensitivity was observed after treatment with ATM inhibitors perhaps due to the decreased DNA repair capacity. 53BP1 knockdown cells showed the higher clonogenic survival presumably due to the increased homologous recombination. We are currently investigating the rate of homologous recombination in this system using a reporter gene and I-SceI induced DNAdsb repair.
