title: OGG1 is essential in oxidative stress induced DNA demethylation.
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.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Changzhou No. 7 People's Hospital, Changzhou 213011, China; School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou 213011, China.
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: He
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Pan
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing 210023, China.
authors.forename: Chandra
authors.initials: C
authors.lastname: Sekhar
authors.affiliation: 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.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D018899:CpG Islands; D000073399:DNA Demethylation / Q000187:drug effects; D045647:DNA Glycosylases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D061986:MCF-7 Cells; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C479058:oxoguanine glycosylase 1, human; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: 8-OxoG; DNA demethylation; OGG1; Oxidative stress; TET1