组蛋白去乙酰化酶抑制剂对DNA双链断裂修复路径的作用

DNA双链断裂(double strand breaks, DSBs)对细胞生存是致命的.细胞内非同源末端连接(NHEJ)、重组修复(HDR)、单链退火修复(SSA)和微同源序列末端连接(MMEJ)等通路可竞争性修复DNA双链断裂损伤.在肿瘤细胞DNA中制造难以修复的基因损伤,诱导肿瘤细胞周期中止、坏死和凋亡是临床放、化疗的主要策略.组蛋白去乙酰化酶（histone deacetylase）作为抗肿瘤治疗的新靶标，其抑制剂(histonedeacetylase inhibitors, HDACi)可显著降低肿瘤细胞DSBs修复能力，增强肿瘤细胞的放、化疗敏感性.研究显示，HDACi抑制了肿瘤细胞中具有正确修复倾向的HDR和经典NHEJ通路，具有错误修复倾向的SSA和MMEJ路径也可能牵涉其中.目前，HDACi作用于DSBs修复通路的分子机制已取得较大进展，但仍有许多问题有待阐明.

Effect of Histone Deacetylase Inhibitors on DNA DSB Repair

DNA double strand break (DSB) can be fatal to cells. The non-homologous end joining (NHEJ), homologous direct recombination (HDR), single strand annealing (SSA) and micro-homology mediated end joining (MMEJ) pathways are able to repair DSBs in vivo. A main strategy of clinical radiotherapy and chemotherapy is to induce chromosomal DNA damage that are difficult to repair, thus to cause cell cycle arrest, apoptosis or necrosis in tumor cells. As a new target of anti-tumor medicine, histone deacetylase inhibitor (HDACi) effectively suppresses DSBs repair capacity and sensitize tumor cells to radiotherapy or chemotherapy. Recent research suggested that the error free DSBs repair pathways HDR and classical-NHEJ were suppressed by HDACi in tumor cells, and the error prone SSA and MMEJ pathways might also involved in. Although much progress have acquired on the mechanism of how HDACi affecting DSB repair pathways, there are still many questions need to be elucidated.