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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(histone deacetylase 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.
DNA double strand breaks (DSBs) are lethal to cell survival. Intracellular non-homologous end joining (NHEJ), recombination repair (HDR), single strand annealing repair (SSA) and micro-homologous end- MMEJ) and other pathways can competitively repair DNA double-strand break damage.It is difficult to repair gene damage in tumor cell DNA and induce tumor cell cycle arrest, necrosis and apoptosis is the main strategy of clinical radiotherapy and chemotherapy.Histone deacetylation As a new target of anti-tumor therapy, histone deacetylase (HDACi) can significantly reduce the repair ability of DSBs in tumor cells and enhance the radiosensitization of tumor cells.Studies show that HDACi inhibits tumor cells HDR and classical NHEJ pathways with correct repair tendencies and SSA and MMEJ path with error repair tendency may also be involved.At present, the molecular mechanism of HDACi acting on DSBs repair pathway has made great progress, but there are still many problems to be clarified .