Date of Original Version
The environmental arylamine mutagens are implicated in the etiology of various sporadic human cancers. Arylamine-modified dG lesions were studied in two fully paired 11-mer duplexes with a -G*C N- sequence context, in which G* is a C8-substituted dG adduct derived from fluorinated analogs of 4-aminobiphenyl (FABP), 2-aminofluorene (FAF) or 2-acetylaminofluorene (FAAF), and N is either dA or dT. The FABP and FAF lesions exist in a simple mixture of ‘stacked’ (S) and ‘B-type’ (B) conformers, whereas the N-acetylated FAAF also samples a ‘wedge’ (W) conformer. FAAF is repaired three to four times more efficiently than FABP and FAF. A simple A- to -T polarity swap in the G*C A/G*CT transition produced a dramatic increase in syn-conformation and resulted in 2- to 3-fold lower nucleotide excision repair (NER) efficiencies in Escherichia coli. These results indicate that lesion-induced DNA bending/thermodynamic destabilization is an important DNA damage recognition factor, more so than the local S/B-conformational heterogeneity that was observed previously for FAF and FAAF in certain sequence contexts. This work represents a novel 3'-next flanking sequence effect as a unique NER factor for bulky arylamine lesions in E. coli.
Jain, Vipin, Benjamin Hilton, Bin Lin, Satyakam Patnailk, Fengting Liang, Eva Darian, You Zhou, Alexander D. Macherell Jr. and Bongsup P. Cho. ʺUnusual Sequence Effects on Nucleotide Excision Repair of Arylamine Lesions: DNA Pending/Distortion as a Primary Recognition Factor.ʺ Nucleic Acids Research. 41(2):869-880. January 2013.
Available at: http://dx.doi.org/10.1093/nar/gks1077
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