Conformational heterogeneity of aminofluorene-DNA adduct at polymerase active site 1 Insights into the Conformation of Aminofluorene-dG Adduct in a DNA Polymerase Active Site
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Crystal structures of 2-acetylaminofluorene and 2-aminofluorene in complex with T7 DNA polymerase reveal mechanisms of mutagenesis.
The carcinogen 2-acetylaminofluorene forms two major DNA adducts: N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and its deacetylated derivative, N-(2'-deoxyguanosin-8-yl)-2-aminofluorene (dG-AF). Although the dG-AAF and dG-AF adducts are distinguished only by the presence or absence of an acetyl group, they have profoundly different effects on DNA replication. dG-AAF poses a strong b...
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Benzo[a]pyrene (BP) is a well-known and frequently encountered carcinogen which generates a bulky DNA adduct (+)-trans-10S-BP-N(2)-dG (BP-dG) in cells. DNA polymerase kappa (polκ) is the only known Y-family polymerase that bypasses BP-dG accurately and thus protects cells from genotoxic BP. Here, we report the structures of human polκ in complex with DNA containing either a normal guanine (G) b...
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Fluorescence spectroscopy was used to study carcinogen-induced conformational heterogeneity in DNA duplexes. The fluorophore 2-aminopurine (AP) was incorporated adjacent (5') to the lesion (G*) in eight different DNA duplexes [d(5'-CTTCT PG* NCCTC-3'):d(5'-GAGGN XTAGAAG-3'), G* = FAF adduct, P = AP, N = G, A, C, T, and X = C, A] modified by FAF [ N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluore...
متن کاملCarcinogenic adducts induce distinct DNA polymerase binding orientations
DNA polymerases must accurately replicate DNA to maintain genome integrity. Carcinogenic adducts, such as 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF), covalently bind DNA bases and promote mutagenesis near the adduct site. The mechanism by which carcinogenic adducts inhibit DNA synthesis and cause mutagenesis remains unclear. Here, we measure interactions between a DNA polymerase an...
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Adduct-induced DNA damage can affect transcription efficiency and DNA replication and repair. We previously investigated the effects of the 3′-next flanking base (G*CT vs G*CA; G*, FABP, N-(2′-deoxyguanosin-8-yl)-4′fluoro-4-aminobiphenyl; FAF, N-(2′-deoxyguanosin-8-yl)-7fluoro-2-aminofluorene) on the conformation of arylamineDNA lesions in relation to E. coli nucleotide excision repair (Jain, V...
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