PIG3의 비상동결합 활성조절 연구

Abstract

The Tumor suppressor protein p53-Inducing gene3 (PIG3) recently has been reported to be a new player in DNA damage signaling and response, but it was not clear that the mechanism involved in DNA repair pathway. In this study, we sought to elucidate molecular mechanism of PIG3-related DNA double strand breaks repair. We show that depletion of endogenous PIG3 sensitizes cells to DNA damage agents such as IR, bleomycin and UV. Comet assay and remaining γ-H2AX show that knockdown of PIG inhibits DNA repair. In addition, PIG3-depleted cells show defect of non-homologous end joining (NHEJ) but not ho-mologous recombination (HR). Moreover, PIG3 is associated with non-homologous end joining related protein including Ku70, Ku80 and DNA-PK in vivo. Especially, Ku70 directly interacts with PIG, suggesting a possible link be-tween a cancer and DNA repair, co-immunoprecipitation analyses revealed that the PIG segment comprising amino acids 201-250 is critical for PIG-Ku70 in-teraction. Therefore, these results suggest that PIG contributes to non-homologous end joining of the DNA damage response through interaction with Ku70.