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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
1999-9-7
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-150600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-1549126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-1566071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-1751545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-1773792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-1944352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-1991121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-2009322,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-2027747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-2679549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-2903446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-2981433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-3034598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-3140380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-3319582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-3890710,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-5263752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-6929024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-6938973,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7501459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7515054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7516181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7623816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7767996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7877977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7958836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-7979257,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8052667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8092677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8202546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8288627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8434126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8479737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8634082,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8635688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8692919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-8961932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-9129943,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-9580699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10454620-9819223
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1362-4962
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3213-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10454620-Base Sequence,
pubmed-meshheading:10454620-Binding Sites,
pubmed-meshheading:10454620-Consensus Sequence,
pubmed-meshheading:10454620-DNA,
pubmed-meshheading:10454620-DNA Damage,
pubmed-meshheading:10454620-DNA Footprinting,
pubmed-meshheading:10454620-DNA Methylation,
pubmed-meshheading:10454620-DNA-Binding Proteins,
pubmed-meshheading:10454620-Deoxyguanine Nucleotides,
pubmed-meshheading:10454620-Humans,
pubmed-meshheading:10454620-Mutagenesis, Site-Directed,
pubmed-meshheading:10454620-NF-kappa B,
pubmed-meshheading:10454620-Oxidation-Reduction,
pubmed-meshheading:10454620-Promoter Regions, Genetic,
pubmed-meshheading:10454620-Protein Binding,
pubmed-meshheading:10454620-Response Elements,
pubmed-meshheading:10454620-Sp1 Transcription Factor,
pubmed-meshheading:10454620-Transcription Factor AP-1,
pubmed-meshheading:10454620-Transcription Factors
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pubmed:year |
1999
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pubmed:articleTitle |
Effect of oxidative DNA damage in promoter elements on transcription factor binding.
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pubmed:affiliation |
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park/Research Division, Smithville, TX 78957, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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