N2-Et-dG, an adduct between DNA and the first metabolite of ethanol (acetaldehyde), strongly blocks transcription by RNA polymerases (RNAPs), including mammalian RNAPII and yeast RNAPII, E. coli RNAP, as well as T7 RNAP. All three of the multisubunit RNAPs incorporate a single rNTP residue opposite the N2-Et-dG lesion. The mammalian RNAPII exclusively incorporates cytidine monophosphate (CMP) opposite the N2-Et-dG lesion. The accessory transcription factor TFIIS does not usually act as a lesion bypass factor; instead, it stimulates the polymerase to remove the CMP incorporated opposite the lesion by mammalian RNAPII. N2-Et-dG reduces CTP incorporation by ~1500 fold.
DNA adducts usually occur at a level of 0.1-1 adducts per 108 unmodified DNA bases, which can cause many adverse health effects if not normally repaired. Using microgram amounts of DNA to detect DNA adducts remains challenging due to the
Archives of toxicology, 92(8), 2665-2680 (2018-06-27)
Adductomics is expected to be useful in the characterization of the exposome, which is a new paradigm for studying the sum of environmental causes of diseases. DNA adductomics is emerging as a powerful method for detecting DNA adducts, but reliable
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