Abstract
Cells from patient with Ataxia Telangiectasia are highly sensitive to ionizing radiation. This enhanced radiosensitivity attributes to the defective repair of double-strand DNA breaks (DNAdsb) or the misrepair. DNAdsb are repaired by multiple pathways including homologous recombinatioal repair, Ku-mediated nonhomologous end joining and 53BP1-mediate d nonhomologous end joining. Although ATM is generally considered to contribute to homologous recombination, there are contradictory reports if ATM is involved in nonhomologous end joining or ATM does not contribute to homologous recombination of I-SceI induced DNAdsb. Thus, association of ATM with DNA repair pathways still remains unclear. In this study using a selective ATM inhibitor and RNAi knockdown of 53BP1 in Ku70 defective cells, we examined the expression of repair proteins and the phosphorylation by western blot.
Intriguingly, 53BP1 knockdown cells showed the higher clonogenic survival than that used to be in the parental Ku70 defective cells, presumably due to the increased homologous recombination. The increased radiosensitivity was suppressed after treatment with ATM inhibitors, perhaps due to the decreased DNA repair capacity. We are currently investigating the roles of ATM expression in this enhanced cell survivals.
