Sasaki M S
Radiation Biology Center, Kyoto University, Yoshida-konoecho, Sakyo-ku, Kyoto, Japan.
Int J Radiat Biol. 2009 Jan;85(1):26-47. doi: 10.1080/09553000802641185.
For more than 70 years radiation cytogenetics has continued to be a topic of major concern in relation to the action of radiation on living cells. To date, diverse cytogenetic findings have developed into orderly, quantitative interpretations and have stimulated numerous biophysical models. However, it is generally agreed that any one of the models used alone is still unable to explain all aspects of the observed chromosomal effects. In this review, a large number of radiation-induced chromosome aberration findings from the literature are reassessed with special attention given to the reaction kinetics and the relevant molecular processes.
It is now clear that DNA double-strand breaks (DSB) are an integral component of radiation-induced chromosome aberration. At the nexus of the maintenance of genome integrity, cells are equipped with excellent systems to repair DSB, notably non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). These repair mechanisms are strictly regulated along with the DNA turnover cycle. NHEJ functions in all phases of the cell cycle, whereas HRR has a supplementary role specifically in S/G2 phase, where homologous DNA sequences are available in close proximity. The repair pathways are further regulated by a complex nuclear dynamism, where DSB are sensed and large numbers of repair proteins are recruited and assembled to form a repair complex involving multiple DSB. Considering such DSB repair dynamism, radiation-induced chromosome aberrations could be well understood as DSB-DSB pairwise interactions associated with the NHEJ pathway in all phases of the cell cycle and misrepair of a single DSB associated with the complementary HRR pathway in late S/G2 phase.
70多年来，辐射细胞遗传学一直是辐射对活细胞作用方面的主要关注话题。迄今为止，各种细胞遗传学研究结果已发展为有序的定量解释，并催生了众多生物物理模型。然而，人们普遍认为，单独使用任何一种模型仍无法解释所观察到的染色体效应的所有方面。在本综述中，对文献中大量辐射诱导的染色体畸变研究结果进行了重新评估，特别关注反应动力学和相关分子过程。
现在很清楚，DNA双链断裂（DSB）是辐射诱导染色体畸变的一个不可或缺的组成部分。在维持基因组完整性的关键环节，细胞配备了出色的DSB修复系统，特别是非同源末端连接（NHEJ）和同源重组修复（HRR）。这些修复机制随着DNA周转周期受到严格调控。NHEJ在细胞周期的所有阶段发挥作用，而HRR则专门在S/G2期发挥补充作用，此时同源DNA序列在附近可用。修复途径进一步受到复杂的核动态变化的调控，在这种变化中，DSB被感知，大量修复蛋白被招募并组装形成涉及多个DSB的修复复合物。考虑到这种DSB修复动态变化，辐射诱导的染色体畸变可以很好地理解为在细胞周期所有阶段与NHEJ途径相关的DSB-DSB成对相互作用，以及在S/G2晚期与互补的HRR途径相关的单个DSB的错误修复。
