title: OGG1-DNA interactions facilitate NF-κB binding to DNA targets.
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-κB 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-κB binding to DNA. Furthermore, OGG1 is essential for NF-κB 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-κB DNA occupancy and gene expression.
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Pan
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Hao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Adeel
authors.initials: A
authors.lastname: Ahmed Abbasi
authors.affiliation: Department of Microbiology and Immunology, Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D016328:NF-kappa B; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D003849:Deoxyguanosine