Abstract
Radiosensitivity attributes to the defective repair of double-strand DNA breaks (DNAdsb) or the misrepair. DNAdsb are repaired by recombinational repair (HR) and nonhomologous end joining (NHEJ). NHEJ is dominant to repair of ionizing radiation induced DNAdsb in mammalian cells. HR pathway accelerates when NHEJ pathway is inhibited. ATM is contributed to HR.
In this study, we examined the role of ATM in DNAdsb repair pathway using Ku70 defective cells and RNAi knockdown of 53BP1 in Ku70 defective cells.
When cells were irradiated at higher dose, radiation resistant fraction was observed in survival curve. This resistant fraction was suppressed in ATM inhibited cells. This indicates that ATM dependent process was needed to repair lesions induced by higher dose irradiation. This result was confirmed as activation of ATM by western blotting. We are currently investigating the rate of homologous recombination in this system using a reporter gene and I-SceI induced DNAdsb repair.
