TOXI 93 |
| The carcinogenic pollutant 2-nitrofluorene produces several DNA adducts including the 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene (dG(N2)-AAF) lesion, a minor adduct that persists for long time in rat tissue DNA after carcinogen administration. We present here the solution structure of a DNA duplex containing a dG(N2)-AAF residue, as determined by NMR spectroscopy and rMD. Spectroscopic data establish a right-handed duplex conformation with Watson-Crick base pair alignments. The AAF moiety resides in the minor grove of the helix where it is directed towards the 5'-end of the modified strand. RMD shows that the duplex structure adjusts locally to the presence of the lesion, reducing exposure of AAF to water. Analysis of UV melting profiles shows that the lesion increases the thermal and thermodynamic stability of DNA, an effect that is driven mainly by favorable entropy. The structure and stability of the dG(N2)-AAF duplex may have important implications for the recognition of bulky lesions by the NER system.
|
|
General Papers
9:00 AM-11:30 AM, Wednesday, 13 September 2006 Moscone Center -- Room 308, Oral
Sci-Mix
Division of Chemical Toxicology |
