Document Type
Article
Date of Original Version
4-2009
Department
Biomedical and Pharmaceutical Sciences
Abstract
When positioned opposite to a dA in a DNA duplex, the prototype arylamine-DNA adduct [N-(2'-deooxyguanosin-yl)-7-flouro-2-aminoflourene(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*NAN dA mismatch duplexes (G*=FAF, N=G, A, C, T) exhibited strongly positive induced circular dichroism in the 290-360nm range (ICD290-360nm), which supports the W conformation. The ICD290-360nm 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 19F 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 ICD260-360 on both temperature and salt concentration and could be extended to the arylamine food mutagens that are biologically relevant in humans.
Citation/Publisher Attribution
Nidhi Jain, Srinivasarao Meneni, Vipin Jain, Bongsup P. Cho; Influence of flanking sequence context on the conformational flexibility of aminofluorene-modified dG adduct in dA mismatch DNA duplexes, Nucleic Acids Research, Volume 37, Issue 5, 1 April 2009, Pages 1628–1637, https://doi.org/10.1093/nar/gkn1063
Available at: http://dx.doi.org/10.1093/nar/gkn1063
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This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Publisher Statement
© 2009 The Author(s)