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Oxidative Damage and Promoter Function

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Oxidative Damage to Nucleic Acids

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

Evidence is accumulating that base damage, particularly that produced by oxidation reactions, can modulate DNA protein interactions and affect promoter function. Such lesions have the capacity to interfere with normal gene regulation through direct interactions with promoter elements, or indirectly by establishing new transcription factor (TF) binding sites. The direct “cis” effects are the most studied and offer the best evidence for oxidative damage interference in promoter function in vitro and in vivo. These studies reveal diverse responses of TF to oxidative damage in promoters that can have either no effect, induce a full or partial inhibition or, in some cases, actually enhance binding depending on the particular TF-promoter system under investigation and the location of the damage within the promoter element. Other, more hypothetical pathways are presented including the de novo production of new consensus binding motifs by oxidative damage/mutations and changes in promoter structure or sequence such that they acquire higher affinity for inappropriate transcription factors. The possibility of molecular hijacking is also discussed.

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Author information

Authors and Affiliations

  1. Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Park Road 1C, Smithville, Texas, 78957, USA

    David Mitchell

  2. Department of Urology, The University of Texas Health Science Center, San Antonio, Texas, USA

    Rita Ghosh

Authors
  1. David Mitchell
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  2. Rita Ghosh
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Editor information

Editors and Affiliations

  1. Radiation and Oxidative Stress Group Department of Cancer Studies and Molecular Medicine RKCSB, Leicester Royal Infirmary, University of Leicester, Leicester, UK

    Mark D. Evans B.Sc., Ph.D.

  2. Department of Cancer Studies and Molecular Medicine and Department of Genetics, University of Leicester, Leicester, UK

    Marcus S. Cooke B.Sc., M.Sc., Ph.D.

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© 2007 Landes Bioscience and Springer Science+Business Media

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Mitchell, D., Ghosh, R. (2007). Oxidative Damage and Promoter Function. In: Evans, M.D., Cooke, M.S. (eds) Oxidative Damage to Nucleic Acids. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72974-9_7

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