Solution conformation of (+)-trans-anti-benzo[a]pyrene-dG adduct positioned at a DNA replication fork junction
Conference
·
OSTI ID:538956
- Memorial Sloan Kettering Cancer Center, New York, NY (United States)
- Oak Ridge National Lab., TN (United States); and others
The solution conformation of the covalent adduct derived from the highly mutagenic (+)-anti-benzo[a]pyrene diol epoxide ((+)-anti-BPDE) at the C10 position to N2 of guanine ((+)-trans-anti-BP-dG) in the d(A1-A2-C3-[BP]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13) .d(G14-G15-A16-T17-G18-G19-T20-A21-G22-C23) 13/10-mer DNA sequence was studied by a combined NMR-molecular mechanics approach. The modified 13-mer strand represents the template strand, while the complementary 10-mer strand models a primer strand which extends up to and is complementary to the modified G4 residue. The pyrenyl ring is directed toward the 5{prime}-end of the template strand and no longer stacks over the adjacent dC5.dG22 base pair, as it does in a 13/9-mer of the same sequence but without the C23 residue. These remarkable differences in the structural motifs of BP-dG lesions at or near single strand-double strand junctions may be important in understanding the effects of BP on DNA replication process.
- OSTI ID:
- 538956
- Report Number(s):
- CONF-960807--
- Country of Publication:
- United States
- Language:
- English
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OSTI ID:5034797