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001-es BibID:BIBFORM069722
Első szerző:Pan, Lang
Cím:Oxidized Guanine Base Lesions Function in 8-Oxoguanine DNA Glycosylase-1-mediated Epigenetic Regulation of Nuclear Factor ?B-driven Gene Expression / Lang Pan, Bing Zhu, Wenjing Hao, Xianlu Zeng, Spiros A. Vlahopoulos, Tapas K. Hazra, Muralidhar L. Hegde, Zsolt Radak, Attila Bacsi, Allan R. Brasier, Xueqing Ba, Istvan Boldogh
Dátum:2016
ISSN:0021-9258 1083-351X
Megjegyzések:A large percentage of redox-responsive gene promoters containevolutionarily conserved guanine-rich clusters; guaninesare the bases most susceptible to oxidative modification(s). Consequently,7,8-dihydro-8-oxoguanine (8-oxoG) is one of themost abundant base lesions in promoters and is primarilyrepaired via the 8-oxoguanine DNA glycosylase-1 (OOG1)-initiatedbase excision repair pathway. In view of a prompt cellularresponse to oxidative challenge, we hypothesized that the8-oxoG lesion and the cognate repair protein OGG1 are utilizedin transcriptional gene activation. Here, we document TNF -induced enrichment of both 8-oxoG and OGG1 in promoters ofpro-inflammatory genes, which precedes interaction of NF- Bwith its DNA-binding motif. OGG1 bound to 8-oxoG upstreamfrom the NF- B motif increased its DNA occupancy by promotingan on-rate of both homodimeric and heterodimeric forms ofNF- B. OGG1 depletion decreased both NF- B binding andgene expression, whereas Nei-like glycosylase-1 and -2 had amarginal effect. These results are the first to document a novelparadigm wherein the DNA repair protein OGG1 bound to itssubstrate is coupled to DNA occupancy of NF- B and functionsin epigenetic regulation of gene expression.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
8-oxoguanine DNA glycosylase1
8-oxoguanine
NF-kappaB
gene expression
inflammation
Megjelenés:Journal Of Biological Chemistry 291 : 49 (2016), p. 25553-25566. -
További szerzők:Zhu, Bing Hao, Wenjing Zeng, Xianlu Vlahopoulos, Spiros A. Hazra, Tapas K. Hegde, Muralidhar L. Radák Zsolt Bácsi Attila (1967-) (immunológus) Brasier, Allan R. Ba, Xueqing Boldogh István
Pályázati támogatás:United States National Institute of Environmental Health and Sciences (grant number: RO1 ES018948 to IB)
Egyéb
United States National Institute of Allergic and Infectious Diseases (grant number: PO1-AI062885, to ARB and IB)
Egyéb
United States National Institute of Environmental Health and Sciences Center Grant (grant number: P30 ES006676 to ARB, IB)
Egyéb
National Science Foundation of China (grant number: 31571339 to XB)
Egyéb
Internet cím:DOI
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