Ionizing radiation exposure results in up-regulation of Ku70 via a p53/ataxia-telangiectasia-mutated protein-dependent mechanism

Genome damaging events, such as gamma-irradiation exposure, result in the i nduction of pathways that activate DNA repair mechanisms, halt cell cycle p rogression, and/or trigger apoptosis. We have investigated the effects of g amma-irradiation on cellular levels of the Ku autoantigens. Ku70 and Ku80 h ave been shown to form a heterodimeric complex that can bind tightly to fre e DNA ends and activate the protein kinase DNA-PKcs, We have found that irr adiation results in an up-regulation of cellular levels of Ku70, but not Ku 80, and that this enhanced level of Ku70 accumulates within the nucleus. Fu rther, we uncovered that the postirradiation up-regulation of Ku70 utilizes a mechanism that is dependent on both p53 and damage response protein kina se ATM (ataxia-telangiectasia-mutated); however, the activation of DNA-PK d oes not require Ku70 up regulation. These findings suggest that Ku70 up-reg ulation provides the cell with a means of assuring either proper DNA repair or an appropriate response to DNA damage independent of DNA-PKcs activatio n.