Structural alignments of (+)- and (-)-trans-anti-benzo[a]pyrene-dG adducts positioned at a DNA template-primer junction
- Memorial Sloan Kettering Cancer Center, New York, NY (United States)
- Oak Ridge National Lab., TN (United States)
- New York Univ., NY (United States); and others
The structural features of a chemically modified DNA template strand may promote error-prone DNA synthesis during replication. The resulting higher incidence of mutations, in turn, can eventually lead to tumor initiation. Structural insights into this process can be monitored by studying chemically modified base adducts of defined-stereochemistry positioned site-specifically at a single strand-duplex template-primer junction. We have used a NMR-molecular mechanics approach to obtain the solution conformations of the covalent adducts derived from trans additions at the [BP]C{sup 10} position of the highly tumorigenic (+)-anti-benzo[a]pyrene diol epoxide [(+)-anti-BPDE] and nontumorigenic (-)-anti-benzo-[a]pyrene diol epoxide [(-)-anti-BPDE] to the N{sup 2} position of guanine [(+) and (-)-trans-anti-[BP]dG, respectively] in the d(Al-A2-C3-[BP]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13){center_dot}(G14-G15-A16-T17-G 18-G19-T20-A21-G22) 13/9-mer DNA sequence. The modified 13-mer strand constitutes the template strand, while the complementary 9-mer strand constitutes a primer which has been synthesized from the 3{prime}-end of the template toward the 5{prime}-end up to the base preceding, but not including, the modified guanine. The modified guanine (denoted by [BP]dG4) is positioned at the junction site between the single-stranded and duplex segments. Structural features of the (+)-trans-anti-[BP]dG 13/9-mer have been determined by incorporating proton-proton distances defined by lower and upper bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. 58 refs., 9 figs., 5 tabs.
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-84OR21400; FG02-90ER60931
- OSTI ID:
- 432163
- Journal Information:
- Biochemistry (Eaton), Vol. 34, Issue 46; Other Information: PBD: 21 Nov 1995
- Country of Publication:
- United States
- Language:
- English
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