Arsenic is an established human carcinogen that can induce DNA damage; however, the precise mechanism remains unknown. Histone modification is of great significance in chemical toxicity and carcinogenesis. To investigate the role of histone H3K9me2 in arsenic-induced DNA damage, HaCaT cells were exposed to sodium arsenite in this study, and the results showed that the enrichment level of H3K9me2 at the N-methylated purine-DNA-glycosylase (MPG), X-ray repair cross-complementary gene 1 (XRCC1), and polyadenylate diphosphate ribose polymerase-1 (PARP1) promoter regions of base-excision repair (BER) genes was increased, which inhibited the expression of these BER genes, thereby inhibiting the repair of DNA damage and aggravating the DNA damage. Furthermore, the molecular mechanism by which H3K9me2 participates in the BER repair of arsenic-induced DNA damage was verified based on functional loss and gain experiments. In addition, Ginkgo biloba extract can upregulate the expression of MPG, XRCC1, and PARP1 and ameliorate cell DNA damage by reducing the enrichment of H3K9me2 at repair gene promoter regions.

中文翻译：

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H3K9me2调控碱基切除修复基因在砷致HaCaT细胞DNA损伤修复中的作用及银杏叶提取物干预的作用

砷是一种公认​​的人类致癌物，可诱导 DNA 损伤；然而，确切的机制仍然未知。组蛋白修饰在化学毒性和致癌作用方面具有重要意义。为了研究组蛋白 H3K9me2 在砷诱导的 DNA 损伤中的作用，本研究将 HaCaT 细胞暴露于亚砷酸钠，结果表明 H3K9me2 在 N-甲基化嘌呤-DNA-糖基化酶 (MPG)、X -射线修复交叉互补基因1（XRCC1）和碱基切除修复（BER）基因的聚腺苷酸二磷酸核糖聚合酶-1（PARP1）启动子区域增加，抑制了这些BER基因的表达，从而抑制了修复DNA 损伤和加重 DNA 损伤。此外，基于功能丧失和获得实验验证了 H3K9me2 参与砷诱导的 DNA 损伤的 BER 修复的分子机制。此外，银杏叶提取物可以通过减少修复基因启动子区域 H3K9me2 的富集，上调 MPG、XRCC1 和 PARP1 的表达并改善细胞 DNA 损伤。