Institute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2094 Xie-Tu Road, Shanghai, 200032, China.
Institute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2094 Xie-Tu Road, Shanghai, 200032, China.
Mutat Res Rev Mutat Res. 2021 Jan-Jun;787:108362. doi: 10.1016/j.mrrev.2020.108362. Epub 2020 Dec 13.
Radiotherapy is one of the primary modalities for cancer treatment, and its efficiency usually relies on cellular radiosensitivity. DNA damage repair is a core content of cellular radiosensitivity, and the primary mechanism of which includes non-homologous end-joining (NHEJ) and homologous recombination (HR). By affecting DNA damage repair, histone methylation regulated by histone methyltransferases (HMTs) and histone demethylases (HDMs) participates in the regulation of cellular radiosensitivity via three mechanisms: (a) recruiting DNA repair-related proteins, (b) regulating the expressions of DNA repair genes, and (c) mediating the dynamic change of chromatin. Interestingly, both aberrantly high and low levels of histone methylation could impede DNA repair processes. Here we reviewed the mechanisms of the dual effects of histone methylation on cell response to radiation. Since some inhibitors of HMTs and HDMs are reported to increase cellular radiosensitivity, understanding their molecular mechanisms may be helpful in developing new drugs for the therapy of radioresistant tumors.
放射疗法是癌症治疗的主要方法之一，其疗效通常依赖于细胞放射敏感性。DNA 损伤修复是细胞放射敏感性的核心内容，其主要机制包括非同源末端连接（NHEJ）和同源重组（HR）。通过影响 DNA 损伤修复，受组蛋白甲基转移酶（HMTs）和组蛋白去甲基化酶（HDMs）调控的组蛋白甲基化通过三种机制参与细胞放射敏感性的调节：（a）招募 DNA 修复相关蛋白，（b）调节 DNA 修复基因的表达，以及（c）介导染色质的动态变化。有趣的是，组蛋白甲基化水平过高或过低都会阻碍 DNA 修复过程。本文综述了组蛋白甲基化对细胞辐射反应的双重作用机制。由于一些 HMTs 和 HDMs 的抑制剂被报道可增加细胞放射敏感性，因此了解其分子机制可能有助于开发治疗耐辐射肿瘤的新药。
