title: Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor.
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.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA.
authors.forename: Vipin
authors.initials: V
authors.lastname: Jain
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hilton
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.forename: Satyakam
authors.initials: S
authors.lastname: Patnaik
authors.forename: Fengting
authors.initials: F
authors.lastname: Liang
authors.forename: Eva
authors.initials: E
authors.lastname: Darian
authors.forename: Yue
authors.initials: Y
authors.lastname: Zou
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Mackerell
authors.forename: Bongsup P
authors.initials: BP
authors.lastname: Cho
mesh_terms: D015073:2-Acetylaminofluorene / Q000737:chemistry*; D000611:Aminobiphenyl Compounds / Q000737:chemistry*; D001483:Base Sequence; D002942:Circular Dichroism; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000378:metabolism; D005449:Fluorenes / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D000611:Aminobiphenyl Compounds; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D005449:Fluorenes; C539832:N-(2'-deoxyguanosinyl)-7-fluoro-2-aminofluorene; C006757:4-biphenylamine; D015073:2-Acetylaminofluorene; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC; D003849:Deoxyguanosine