Influence of flanking sequence context on the conformational flexibility of aminofluorene-modified dG adduct in dA mismatch DNA duplexes.
When positioned opposite to a dA in a DNA duplex, the prototype arylamine-DNA adduct [N-(2'-deoxyguanosin-yl)-7-fluoro-2-aminofluorene (FAF)] adopts the so-called 'wedge' (W) conformation, in which the carcinogen resides in the minor groove of the duplex. All 16 FAF-modified 12-mer NG*N/NAN dA mismatch duplexes (G* = FAF, N = G, A, C, T) exhibited strongly positive induced circular dichroism in the 290-360 nm range (ICD(290-360 nm)), which supports the W conformation. The ICD(290-360 nm) intensities were the greatest for duplexes with a 3'-flanking T. The AG*N duplex series showed little adduct-induced destabilization. An exception was the AG*T duplex, which displayed two well-resolved signals in the (19)F NMR spectra. This was presumably due to a strong lesion-destabilizing effect of the 3'-T. The flanking T effect was substantiated further by findings with the TG*T duplex, which exhibited greater lesion flexibility and nucleotide excision repair recognition. Adduct conformational heterogeneity decreased in order of TG*T > AG*T > CG*T > AG*A > AG*G > AG*C. The dramatic flanking T effect on W-conformeric duplexes is consistent with the strong dependence of the ICD(290-360) on both temperature and salt concentration and could be extended to the arylamine food mutagens that are biologically relevant in humans.
Jain
Nidhi
N
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Meneni
Srinivasarao
S
Jain
Vipin
V
Cho
Bongsup P
BP
D020137:Base Pair Mismatch; D001483:Base Sequence; D002942:Circular Dichroism; D018736:DNA Adducts / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D012965:Sodium Chloride; D013696:Temperature
D018736:DNA Adducts; D003839:Deoxyadenosines; D005449:Fluorenes; C539832:N-(2'-deoxyguanosinyl)-7-fluoro-2-aminofluorene; D012965:Sodium Chloride; D003849:Deoxyguanosine