Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity.
Traditional radiobiology has aimed at elucidating the mechanism of radiosensitivity of cancer cells and normal cells. Because the mechanism of DNA double-strand break (DSB) repair, which is inherently important to radiosensitivity, was unknown, it has been difficult to obtain results applicable to clinical radiotherapy from traditional radiobiology research. Today, however, the molecular mechanism of DNA DSB repair has been elucidated because of the rapid advances in molecular biology. In DNA DSB repair, at least two major repair mechanisms, homologous recombination and nonhomologous end joining (NHEJ) have been reported. In the 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 DSB repair by NHEJ. We have investigated how the ability of repair of DNA DSB influences cancer susceptibility and the radiosensitivity of tumors and normal tissues by focusing on the activity of DNA-PK. In the near future, research on DNA DSB repair mechanism will be able to be applied to research on carcinogenesis, prediction of radiosensitivity of tumors and normal cells, and sensitization of tumor cells.
Sakata
Koh-Ichi
K
Department of Radiology, Sapporo Medical University School of Medicine, West 16, North 1, Chuo-ku, Sapporo 060-8543, Japan. akatako@sapmed.ac.jp
Someya
Masanori
M
Matsumoto
Yoshihisa
Y
Hareyama
Masato
M
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics*; D011995:Recombination, Genetic
D051747:DNA-Activated Protein Kinase