Back to Search
Start Over
Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor
- Source :
- Nucleic Acids Research
- Publication Year :
- 2012
- Publisher :
- Oxford University Press (OUP), 2012.
-
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.
- Subjects :
- Models, Molecular
DNA Repair
DNA repair
DNA damage
Electrophoretic Mobility Shift Assay
Context (language use)
Molecular Dynamics Simulation
Genome Integrity, Repair and Replication
Biology
010402 general chemistry
01 natural sciences
DNA Adducts
03 medical and health sciences
chemistry.chemical_compound
Escherichia coli
Genetics
Aminobiphenyl Compounds
Electrophoretic mobility shift assay
Nuclear Magnetic Resonance, Biomolecular
030304 developmental biology
Fluorenes
0303 health sciences
Endodeoxyribonucleases
Base Sequence
Transition (genetics)
Circular Dichroism
Escherichia coli Proteins
Deoxyguanosine
2-Acetylaminofluorene
Molecular biology
0104 chemical sciences
chemistry
Biochemistry
Nucleic Acid Conformation
Thermodynamics
DNA
DNA Damage
Nucleotide excision repair
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....f479cd0461b955108f908d5435152748