Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity.
Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity.
复制标题
DOI：
10.1007/s11604-007-0161-3
复制
发表时间：
2007-11-01
影响因子：
--
通讯作者：
Hareyama, Masato
中科院分区：
文献类型：
--
作者：
Sakata, Koh-Ichi;Someya, Masanori;Hareyama, Masato
传统的放射生物学旨在阐明癌细胞和正常细胞的放射敏感性机制。由于DNA双链断裂（DSB）修复机制对放射敏感性的内在重要性尚不清楚，传统的放射生物学研究难以获得适用于临床放射治疗的结果。然而，今天，由于分子生物学的快速发展，DNA DSB修复的分子机制已经被阐明。在DNA DSB修复中，至少有两种主要的修复机制，同源重组和非同源末端连接（NHEJ）。在NHEJ途径中，DSB直接或在DNA末端加工后在适当的染色体末端重新连接。DNA依赖性蛋白激酶（DNA-PK）在NHEJ修复DNA双链断裂中起重要作用。我们已经研究了DNA DSB的修复能力如何影响癌症的易感性和肿瘤和正常组织的放射敏感性，通过关注DNA-PK的活性。在不久的将来，DNA双链断裂修复机制的研究将可应用于肿瘤发生机制的研究、肿瘤和正常细胞放射敏感性的预测以及肿瘤细胞的增敏。
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.