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• W2127761639 endingPage "3218" @default.
• W2127761639 startingPage "3213" @default.
• W2127761639 abstract "Reactive oxygen species produced by endogenous metabolic activity and exposure to a multitude of exogenous agents impact cells in a variety of ways. The DNA base damage 8-oxodeoxyguanosine (8-oxodG) is a prominent indicator of oxidative stress and has been well-characterized as a premutagenic lesion in mammalian cells and putative initiator of the carcinogenic process. Commensurate with the recent interest in epigenetic pathways of cancer causation we investigated how 8-oxodG alters the interaction between cis elements located on gene promoters and sequence-specific DNA binding proteins associated with these promoters. Consensus binding sequences for the transcription factors AP-1, NF-kappaB and Sp1 were modified site-specifically at guanine residues and electrophoretic mobility shift assays were performed to assess DNA-protein interactions. Our results indicate that whereas a single 8-oxodG was sufficient to inhibit transcription factor binding to AP-1 and Sp1 sequences it had no effect on binding to NF-kappaB, regardless of its position. We conclude from these data that minor alterations in base composition at a crucial position within some, but not all, promoter elements have the ability to disrupt transcription factor binding. The lack of inhibition by damaged NF-kappaB sequences suggests that DNA-protein contact sites may not be as determinative for stable p50 binding to this promoter as other, as yet undefined, structural parameters." @default.
• W2127761639 created "2016-06-24" @default.
• W2127761639 creator A5055705058 @default.
• W2127761639 creator A5060082494 @default.
• W2127761639 date "1999-08-01" @default.
• W2127761639 modified "2023-10-01" @default.
• W2127761639 title "Effect of oxidative DNA damage in promoter elements on transcription factor binding" @default.
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• W2127761639 doi "https://doi.org/10.1093/nar/27.15.3213" @default.
• W2127761639 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/148550" @default.
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• W2127761639 hasPublicationYear "1999" @default.
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