Institute of Environmental Systems Biology, College of Environmental Science and Engineering, Dalian Maritime University, Dalian, 116026 Liaoning, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Biomed Res Int. 2020 Aug 25;2020:4834965. doi: 10.1155/2020/4834965. eCollection 2020.
Ionising radiation- (IR-) induced DNA double-strand breaks (DSBs) are considered to be the deleterious DNA lesions that pose a serious threat to genomic stability. The major DNA repair pathways, including classical nonhomologous end joining, homologous recombination, single-strand annealing, and alternative end joining, play critical roles in countering and eliciting IR-induced DSBs to ensure genome integrity. If the IR-induced DNA DSBs are not repaired correctly, the residual or incorrectly repaired DSBs can result in genomic instability that is associated with certain human diseases. Although many efforts have been made in investigating the major mechanisms of IR-induced DNA DSB repair, it is still unclear what determines the choices of IR-induced DNA DSB repair pathways. In this review, we discuss how the mechanisms of IR-induced DSB repair pathway choices can operate in irradiated cells. We first briefly describe the main mechanisms of the major DNA DSB repair pathways and the related key repair proteins. Based on our understanding of the characteristics of IR-induced DNA DSBs and the regulatory mechanisms of DSB repair pathways in irradiated cells and recent advances in this field, We then highlight the main factors and associated challenges to determine the IR-induced DSB repair pathway choices. We conclude that the type and distribution of IR-induced DSBs, chromatin state, DNA-end structure, and DNA-end resection are the main determinants of the choice of the IR-induced DNA DSB repair pathway.
电离辐射（IR）诱导的 DNA 双链断裂（DSBs）被认为是对基因组稳定性构成严重威胁的有害 DNA 损伤。包括经典的非同源末端连接、同源重组、单链退火和替代性末端连接在内的主要 DNA 修复途径在应对和引发 IR 诱导的 DSB 以确保基因组完整性方面发挥着关键作用。如果 IR 诱导的 DNA DSB 不能正确修复，残留的或不正确修复的 DSB 可能导致与某些人类疾病相关的基因组不稳定性。尽管人们在研究 IR 诱导的 DNA DSB 修复的主要机制方面做出了许多努力，但仍不清楚是什么决定了 IR 诱导的 DNA DSB 修复途径的选择。在这篇综述中，我们讨论了 IR 诱导的 DSB 修复途径选择的机制如何在照射细胞中起作用。我们首先简要描述了主要 DNA DSB 修复途径的主要机制以及相关的关键修复蛋白。基于我们对 IR 诱导的 DNA DSB 特征以及照射细胞中 DSB 修复途径的调控机制的理解，并结合该领域的最新进展，我们随后强调了决定 IR 诱导的 DSB 修复途径选择的主要因素和相关挑战。我们得出的结论是，IR 诱导的 DSB 的类型和分布、染色质状态、DNA 末端结构和 DNA 末端切除是 IR 诱导的 DNA DSB 修复途径选择的主要决定因素。
