@article{afb8bfb7ce4f469e89dabd5fa1c87e58,
title = "Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription",
abstract = "8-Oxoguanine DNA glycosylase1 (OGG1)-initiated base excision repair (BER) is the primary pathway to remove the pre-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Recent studies documented 8-oxoG serves as an epigenetic-like mark and OGG1 modulates gene expression in oxidatively stressed cells. For this new role of OGG1, two distinct mechanisms have been proposed: one is coupled to base excision, while the other only requires substrate binding of OGG1––both resulting in conformational adjustment in the adjacent DNA sequences providing access for transcription factors to their cis-elements. The present study aimed to examine if BER activity of OGG1 is required for pro-inflammatory gene expression. To this end, Ogg1/OGG1 knockout/depleted cells were transfected with constructs expressing wild-type (wt) and repair-deficient mutants of OGG1. OGG1's promoter enrichment, oxidative state, and gene expression were examined. Results showed that TNFα exposure increased levels of oxidatively modified cysteine(s) of wt OGG1 without impairing its association with promoter and facilitated gene expression. The excision deficient K249Q mutant was even a more potent activator of gene expression; whereas, mutant OGG1 with impaired substrate recognition/binding was not. These data suggested the interaction of OGG1 with its substrate at regulatory regions followed by conformational adjustment in the adjacent DNA is the primary mode to modulate inflammatory gene expression.",
keywords = "8-oxoG, OGG1, oxidative stress, pro-inflammatory gene expression",
author = "Wenjing Hao and Jing Wang and Yuanhang Zhang and Chenxin Wang and Lan Xia and Wenhe Zhang and Muhammad Zafar and Kang, {Ju Yong} and Ruoxi Wang and {Ali Bohio}, Ameer and Lang Pan and Xianlu Zeng and Min Wei and Istvan Boldogh and Xueqing Ba",
note = "Funding Information: For editing this manuscript, we thank Sherry L. Haller, PhD, English Editor, Research Development Specialist, The University of Texas Medical Branch, Galveston, TX. USA. This research was supported by grants from the National Natural Science Foundation of China, grant no. 31571339, 31970686 to XB, and 31900557 to RW, the Program for Introducing Talent to Universities, grant no. B07017 to XB, and grants from United States National Institute of Environmental Health and Sciences, grant no. RO1 ES018948 to IB, United States National Institute of Allergic and Infectious Diseases, grant no. AI062885 to IB. Funding Information: For editing this manuscript, we thank Sherry L. Haller, PhD, English Editor, Research Development Specialist, The University of Texas Medical Branch, Galveston, TX. USA. This research was supported by grants from the National Natural Science Foundation of China, grant no. 31571339, 31970686 to XB, and 31900557 to RW, the Program for Introducing Talent to Universities, grant no. B07017 to XB, and grants from United States National Institute of Environmental Health and Sciences, grant no. RO1 ES018948 to IB, United States National Institute of Allergic and Infectious Diseases, grant no. AI062885 to IB. Publisher Copyright: {\textcopyright} 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology",
year = "2020",
month = jun,
day = "1",
doi = "10.1096/fj.201902243R",
language = "English (US)",
volume = "34",
pages = "7427--7441",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "6",
}