The role of H3K9me2-regulated base excision repair genes in the repair of DNA damage induced by arsenic in HaCaT cells and the effects of Ginkgo biloba extract intervention
The role of H3K9me2-regulated base excision repair genes in the repair of DNA damage induced by arsenic in HaCaT cells and the effects of Ginkgo biloba extract intervention
复制标题
H3K9me2调控的碱基切除修复基因在砷诱导的HaCaT细胞DNA损伤修复中的作用及银杏叶提取物的干预作用
DOI：
10.1002/tox.23088
复制
发表时间：
2020-12-30
影响因子：
4.5
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Ding, Xuejiao;Zhang, Anliu;Li, Jun
砷是一种公认的人类致癌物，可诱导DNA损伤;然而，确切的机制仍不清楚。组蛋白修饰在化学毒性和致癌作用中具有重要意义。为探讨组蛋白H3 K9 me 2在砷诱导的DNA损伤中的作用，本研究采用亚砷酸钠处理HaCaT细胞，结果显示，H3 K9 me 2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（XRCC 1）、碱基切除修复（BER）基因的多聚腺苷酸二磷酸核糖聚合酶-1（PARP 1）启动子区增加，从而抑制这些BER基因的表达，从而抑制DNA损伤的修复，加重DNA损伤。此外，通过功能丧失和获得实验，验证了H3 K9 me 2参与砷诱导的DNA损伤的BER修复的分子机制。此外，银杏叶提取物可以上调MPG，XRCC 1和PARP 1的表达，并通过减少H3 K9 me 2在修复基因启动子区的富集来改善细胞DNA损伤。
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.