Unusual Sequence Effects on Nucleotide Excision Repair of Arylamine Lesions: DNA Bending/Distortion as a Primary Recognition Factor
Document Type
Article
Publication Date
1-1-2013
Description
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*CN-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*CA/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.
Citation Information
Jain, Vipin; Hilton, Benjamin; Lin, Bin; Patnaik, Satyakam; Liang, Fengting; Darian, Eva; Zou, Yue; MacKerell, Alexander D.; and Cho, Bongsup P.. 2013. Unusual Sequence Effects on Nucleotide Excision Repair of Arylamine Lesions: DNA Bending/Distortion as a Primary Recognition Factor. Nucleic Acids Research. Vol.41(2). 869-880. https://doi.org/10.1093/nar/gks1077 PMID: 23180767 ISSN: 0305-1048