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Cell Signal. 2016 Sep;28(9):1163-71. doi: 10.1016/j.cellsig.2016.05.021. Epub 2016 May 29.

OGG1 is essential in oxidative stress induced DNA demethylation.

Author information

1
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
2
Changzhou No. 7 People's Hospital, Changzhou 213011, China; School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou 213011, China.
3
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China. Electronic address: guozgang@gmail.com.

Abstract

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.

KEYWORDS:

8-OxoG; DNA demethylation; OGG1; Oxidative stress; TET1

PMID:
27251462
DOI:
10.1016/j.cellsig.2016.05.021
[Indexed for MEDLINE]

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