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. ATM is contributed to HR. Although relationships of repair pathways still remains unclear, it is reported that 53BP1 work to repair pathway choice. Namely, radiosensitivity increased in BRCA1 defective cells because of HR defective. Radiosensitivity was recovered by 53BP1 knockdown. This was because DNA bound 53BP1 inhibit BRCA1/CtIP. 53BP1 defect induce CtIP mediated resection. HR acceleration is ATM dependent in 53BP1 knockdown BRCA1 defective cells.
In this study, we examined the role of ATM and 53BP1 in DNAdsb repair pathway using RNAi knockdown of 53BP1 in Ku70 defective cells. 53BP1 knockdown cells showed higher survival than that used to be in the parental Ku70 defective cells. Increased radiosensitivity was suppressed after treatment with ATM inhibitors. This indicates that ATM associated HR is accelerated. We are currently investigating the rate of homologous recombination in this system using a reporter gene and I-SceI induced DNAdsb repair.
