Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C(8)-dG adduct positioned at a template-primer junction Journal Article
| Authors: | Mao, B.; Gu, Z.; Gorin, A.; Hingerty, B. E.; Broyde, S.; Patel, D. J. |
| Article Title: | Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C(8)-dG adduct positioned at a template-primer junction |
| Abstract: | A solution structural study has been undertaken on the aminofluorene-C-8-dG ([AF]dG) adduct located at a single strand-double strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13) . d(G14-G15-A16-T17-G18-G19-T20-A21-G22) 13/9-mer junction (designated [AF]dG 13/9-mer) using proton-proton distance and intensity restraints derived from NMR data in combination with a computational protocol, which includes intensity refinement. This single strand-double strand junction models one arm of a replication fork composed of a 13-mer template strand, which contains the [AF]dG modification site, and a 9-mer primer strand, which has been elongated up to, but not including, the modified guanine. The NMR data establish that the duplex segment retains a minimally perturbed B-DNA conformation including Watson-Crick hydrogen-bonding at the junctional dC5.dG22 base pair. The NMR spectra are consistent with the guanine ring of the [AF]dG4 adduct adopting a syn glycosidic torsion angle and being displaced into the major groove with the adjacent dC3 residue displaced into the minor groove. Such a base displacement of the modified guanine is accompanied by stacking of one face of the fluorene ring of [AF]dG4 with the dC5.dG22 base pair, while the other face of the flourene ring is stacked with the purine ring of the nonadjacent dA2 residue in the intensity-refined solution structures of the [AF]dG 13/9-mer. A comparison of structural features of the C-8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N-2-[BP]dG adduct [Cosman et al. (1995) Biochemistry 34, 15334-15350] in the same 13/9-mer junctional sequence context has identified common features associated with the alignment of the modified guanine adducts at the template-primer junction. Thus, despite differences in the covalent linkage site for the C-8-[AF]dG and (+)-trans-anti-N-2-[BP]dG adducts, one face of the aromatic ring of the carcinogen stacks over the junctional base pair and in so doing displaces the modified guanine in a syn alignment into the major groove. These results lend credence to earlier proposals that such an adduct alignment may represent a common mutagenic conformer at a template-primer junction associated with a replication fork. |
| Keywords: | nmr; molecular-dynamics; base displacement; opposite; major groove; 2-acetylaminofluorene; nuclear magnetic-resonance; dna duplex; 2-aminofluorene-modified dna; energy minimization; <af>dg |
| Journal Title: | Biochemistry |
| Volume: | 36 |
| Issue: | 47 |
| ISSN: | 0006-2960 |
| Publisher: | American Chemical Society |
| Date Published: | 1997-11-25 |
| Start Page: | 14491 |
| End Page: | 14501 |
| Language: | English |
| ACCESSION: | WOS:A1997YH56600025 |
| DOI: | 10.1021/bi972206r |
| PROVIDER: | wos |
| PUBMED: | 9398168 |
| Notes: | Article -- Source: Wos |
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