Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10753862 | Biochemical and Biophysical Research Communications | 2014 | 7 Pages |
Abstract
Benzo(a)pyrene (BaP) is a known carcinogen cytotoxic which can trigger extensive cellular responses. Many evidences suggest that inhibitors of poly(ADP-ribose) glycohydrolase (PARG) are potent anticancer drug candidates. However, the role of PARG in BaP carcinogenesis is less understood. Here we used PARG-deficient human bronchial epithelial cell line (shPARG cell) as an in vitro model, and investigated the role of PARG silencing in DNA methylation pattern changed by BaP. Our study shows, BaP treatment decreased global DNA methylation levels in 16HBE cells in a dose-dependent manner, but no dramatic changes were observed in shPARG cells. Further investigation revealed PARG silencing protected DNA methyltransferases (DNMTs) activity from change by BaP exposure. Interestingly, Dnmt1 is PARylated in PARG-null cells after BaP exposure. The results show a role for PARG silencing in DNA hypomethylation induced by BaP that may provide new clue for cancer therapy.
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Authors
Haiyan Huang, Gonghua Hu, Jianfeng Cai, Bo Xia, Jianjun Liu, Xuan Li, Wei Gao, Jianqing Zhang, Yinpin Liu, Zhixiong Zhuang,