| Autor: |
Jain, Vipin, Hilton, Benjamin, Lin, Bin, Patnaik, Satyakam, Liang, Fengting, Darian, Eva, Zou, Yue, MacKerell, Alexander D., Cho, Bongsup P. |
| Předmět: |
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| Zdroj: |
ETSU Faculty Works. |
| Druh dokumentu: |
Text |
| DOI: |
10.1093/nar/gks1077 |
| Popis: |
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. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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