OGG1 is essential in oxidative stress induced DNA demethylation.
OGG1 is essential in oxidative stress induced DNA demethylation.
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DOI：
10.1016/j.cellsig.2016.05.021
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发表时间：
2016-09
影响因子：
4.8
通讯作者：
Xiaolong Zhou;Ziheng Zhuang;Wentao Wang;Lingfeng He;Huan Wu;Yan Cao;Feiyan Pan;Jing Zhao;Zhigang Hu;C. Sekhar;Zhigang Guo
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文献类型：
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作者：
Xiaolong Zhou;Ziheng Zhuang;Wentao Wang;Lingfeng He;Huan Wu;Yan Cao;Feiyan Pan;Jing Zhao;Zhigang Hu;C. Sekhar;Zhigang Guo
DNA去甲基化是调控基因表达的重要细胞活动；然而，触发DNA去甲基化的机制仍然未知。此外，DNA去甲基化最近被证明是由氧化应激诱导的，但没有明确的分子机制。在这篇文章中，我们证明了8-氧鸟嘌呤DNA糖基化酶-1 （OGG1）是参与氧化应激诱导的DNA去甲基化的必需蛋白。氧化应激诱导8-氧鸟嘌呤（8-oxoG）的形成。我们发现8-oxoG结合蛋白OGG1通过相互作用和招募TET1到8-oxoG损伤处来促进DNA去甲基化。OGG1的下调使细胞抵抗氧化应激诱导的DNA去甲基化，而OGG1的过表达使细胞易受氧化应激诱导的DNA去甲基化。这些数据不仅说明了碱基切除修复（BER）在DNA去甲基化中的重要性，而且揭示了DNA去甲基化信号是如何传递到下游DNA去甲基化酶的。
DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8-oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress-induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes.