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Oxidants in signal transduction: impact on DNA integrity and gene expression
Author(s) -
Ziel Kathryn A.,
Grishko Valentina,
Campbell Clayton C.,
Breit Jeffrey F.,
Wilson Glenn L.,
Gillespie Mark N.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2805com
Subject(s) - dna repair , gene expression , dna damage , dna , biology , gene , signal transduction , regulation of gene expression , guanine , coactivator , base excision repair , microbiology and biotechnology , reporter gene , ap site , chemistry , biochemistry , nucleotide , transcription factor
Physiological stimuli using reactive oxygen species (ROS) as second messengers caused nucleotide‐specific base modifications in the hypoxic response element of the VEGF gene in lung vascular cells, with the 3′ guanine of the HIF‐1 DNA recognition sequence uniformly targeted. Modeling this effect by replacing the targeted guanine with an abasic site increased incorporation of HIF‐1 and the bi‐functional DNA repair enzyme and transcriptional coactivator, Ref‐1/Ape1, into the transcriptional complex and engendered more robust reporter gene expression. Oxidants generated in the context of physiological signaling thus affect nuclear DNA integrity and may facilitate gene expression by optimizing DNA‐protein interactions.—Ziel, K. A., Grishko, V., Campbell, C. C., Breit, J. F., Wilson, G. L., Gillespie, M. N. Oxidants in signal transduction: impact on DNA integrity and gene expression. FASEB J. 19, 387‐394 (2005)