2本鎖DNA切断修復研究と臨床応用

Repair of various types of DNA damages are critical for cell survival. Of these, DNA double-strand break (DSB) is believed to be one of the most serious damage induced by DNA damaging agents such as ionizing irradiation. In DNA DSB repair, at least two major repair mechanisms, homologous recombination and non-homologous end-joining (NHEJ) have been reported. In NHEJ pathway, DSBs are directly, or after processing of the DNA ends, rejoined at an appropriate chromosomal end. DNA-dependent protein kinase (DNA-PK) plays an important role in DNA DSBs repair by NHEJ. We have investigated how the ability of repair of DNA double-strand break influences the cancer susceptibility and the radiosensitivity of tumors and normal tissues, by focusing on the activity of DNA-PK. Clinical application of these results about DNA DSB repair will improve results of cancer radiotherapy