Abstract
Upon exposure to ionizing radiation, 53BP1 is rapidly redistributed to sites of DNA double-strand breaks and is hyperphosphorylated in an ATM-dependent manner. In experiments using hyper-recombinogenic chicken B cell line DT40, we revealed that there are at least three sub-pathways in repair of X-ray induced DNA damage: 1) the core non-homologous end-joining (core NHEJ) which is dependent on Ku70/Ku80/DNA-PK, 2) Artemis-dependent pathway which includes ATM, and 3) 53BP1-dependent pathway. A cell-line that is deficient for one of these pathways showed elevated X-ray sensitivity in G1 phase. In contrast to the core NHEJ and Artemis-dependent pathways, the 53BP1-dependent pathway was resistant to PI-3 kinase inhibitor wortmannin. To identify proteins involved in the 53BP1-dependent pathway, we established some DT40 cell-lines that are deficient for one of candidate genes expected to be involved in this pathway, and examined the X-ray sensitivity of these cell-lines in the G1 phase. Among these cell lines, Snm1a-defficient, and Snm1b-deficient cell-lines did not show increase in G1-phase X-ray sensitivity. We are now examining some other genes whose products form foci in response to IR. We would like to present proteins which is involved in the 53BP1-dependent repair pathway.
