OGG1-DNA interactions facilitate NF-k B binding to DNA targets

Lang Pan, Wenjing Hao, Xu Zheng, Xianlu Zeng, Adeel Ahmed Abbasi, Istvan Boldogh, Xueqing Ba

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

DNA repair protein counteracting oxidative promoter lesions may modulate gene expression. Oxidative DNA bases modified by reactive oxygen species (ROS), primarily as 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase1 (OGG1) during base excision repair (BER) pathway. Because cellular response to oxidative challenge is accompanied by DNA damage repair, we tested whether the repair by OGG1 is compatible with transcription factor binding and gene expression. We performed electrophoretic mobility shift assay (EMSA) using wild-type sequence deriving from Cxcl2 gene promoter and the same sequence bearing a single synthetic 8-oxoG at defined 5′ or 3′ guanine in runs of guanines to mimic oxidative effects. We showed that DNA occupancy of NF-k B present in nuclear extracts from tumour necrosis factor alpha (TNFα) exposed cells is OGG1 and 8-oxoG position dependent, importantly, OGG1 counteracting 8-oxoG outside consensus motif had a profound influence on purified NF-k B binding to DNA. Furthermore, OGG1 is essential for NF-k B dependent gene expression, prior to 8-oxoG excised from DNA. These observations imply that pre-excision step(s) during OGG1 initiated BER evoked by ROS facilitates NF-k B DNA occupancy and gene expression.

Original languageEnglish (US)
Article number43297
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 7 2017

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DNA
DNA Repair
Gene Expression
Guanine
Reactive Oxygen Species
Electrophoretic Mobility Shift Assay
DNA Damage
Transcription Factors
Tumor Necrosis Factor-alpha
8-oxo-7-hydrodeoxyguanosine
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Pan, L., Hao, W., Zheng, X., Zeng, X., Ahmed Abbasi, A., Boldogh, I., & Ba, X. (2017). OGG1-DNA interactions facilitate NF-k B binding to DNA targets. Scientific Reports, 7, [43297]. https://doi.org/10.1038/srep43297

OGG1-DNA interactions facilitate NF-k B binding to DNA targets. / Pan, Lang; Hao, Wenjing; Zheng, Xu; Zeng, Xianlu; Ahmed Abbasi, Adeel; Boldogh, Istvan; Ba, Xueqing.

In: Scientific Reports, Vol. 7, 43297, 07.03.2017.

Research output: Contribution to journalArticle

Pan, L, Hao, W, Zheng, X, Zeng, X, Ahmed Abbasi, A, Boldogh, I & Ba, X 2017, 'OGG1-DNA interactions facilitate NF-k B binding to DNA targets', Scientific Reports, vol. 7, 43297. https://doi.org/10.1038/srep43297
Pan, Lang ; Hao, Wenjing ; Zheng, Xu ; Zeng, Xianlu ; Ahmed Abbasi, Adeel ; Boldogh, Istvan ; Ba, Xueqing. / OGG1-DNA interactions facilitate NF-k B binding to DNA targets. In: Scientific Reports. 2017 ; Vol. 7.
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