Abstract
A solution structural study has been undertaken on the aminofluorene- C8-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 C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[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 C8-[AF]dG and (+)-trans-anti-N2-[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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 14491-14501 |
| Number of pages | 11 |
| Journal | Biochemistry |
| Volume | 36 |
| Issue number | 47 |
| DOIs | |
| State | Published - Nov 25 1997 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction. / Mao, Bing; Gu, Zhengtian; Gorin, Andrey; Hingerty, Brian E.; Broyde, Suse; Patel, Dinshaw J.
In: Biochemistry, Vol. 36, No. 47, 25.11.1997, p. 14491-14501.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction
AU - Mao, Bing
AU - Gu, Zhengtian
AU - Gorin, Andrey
AU - Hingerty, Brian E.
AU - Broyde, Suse
AU - Patel, Dinshaw J.
PY - 1997/11/25
Y1 - 1997/11/25
N2 - A solution structural study has been undertaken on the aminofluorene- C8-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 C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[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 C8-[AF]dG and (+)-trans-anti-N2-[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.
AB - A solution structural study has been undertaken on the aminofluorene- C8-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 C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[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 C8-[AF]dG and (+)-trans-anti-N2-[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.
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U2 - 10.1021/bi972206r
DO - 10.1021/bi972206r
M3 - Article
C2 - 9398168
AN - SCOPUS:0030667581
VL - 36
SP - 14491
EP - 14501
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 47
ER -