Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor

Vipin Jain, Benjamin Hilton, Bin Lin, Satyakam Patnaik, Fengting Liang, Eva Darian, Yue Zou, Alexander D. MacKerell, Bongsup P. Cho

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)869-880
Number of pages12
JournalNucleic acids research
Volume41
Issue number2
DOIs
StatePublished - Jan 2013

Bibliographical note

Funding Information:
National Institutes of Health (NIH) [CA098296 to B.C., GM051501 to A.D.M. and CA86927 to Y.Z.]; the National Science Foundation/RI-EPSCoR [0554548] and the RI-INBRE core facility supported by National Institutes of Health [P20 RR016457]. Funding for open access charge: NIH/NCI.

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