Structural studies of the ionizing radiation adduct 7,8-dihydro-8-oxoadenine (A(oxo)) positioned opposite thymine in a DNA duplex Journal Article
| Authors: | Chen, H.; Johnson, F.; Grollman, A. P.; Patel, D. J. |
| Article Title: | Structural studies of the ionizing radiation adduct 7,8-dihydro-8-oxoadenine (A(oxo)) positioned opposite thymine in a DNA duplex |
| Abstract: | The oxidative DNA damage adduct 8-oxo-7H-adenine (Aoxo) has been shown to incorporate T and G in primer extension reactions catalyzed by a range of polymerases. This paper reports on efforts to characterize the Aoxo · T pairing alignment and the structure at and adjacent to the damage site at the DNA duplex level. The solution structure of an d(G1-C2-A3-T4-G5-T6-G7-T8-A9-C10-G11) · d(C12-G13-T14-A15-C16-Aoxo17-C18-A19-T20-G21-C22) undecanucleotide duplex (designated Aoxo · T 11-mer) was determined by a combination of NMR and molecular dynamics calculations including NOE intensity-based refinements. This sequence forms a right-handed duplex in which all residues are in the anti conformation and all base pairs adopt Watson-Crick pairing alignments. The Aoxo17 residue adopts the 6-amino-8-keto tautomeric arrangement and forms a T6(anti) · Aoxo17(anti) Watson-Crick base pair with the opposing T6 residue on the partner strand. The central d(G5-T6-G7) · d(C16-Aoxo17-C18) three base pair segment of the Aoxo · T 11-mer duplex is very well defined in the relaxation matrix refined structures and its conformation establishes that incorporation of the Aoxo lesion into a DNA duplex has little effect on the DNA structure when paired opposite a thymine residue. These results imply that the recognition of Aoxo · T by the repair machinery is likely to originate in the unusual donor-donor-acceptor hydrogen bonding functionalities at the (NH2-6)-NH7-O8 positions along the major groove edge of the Aoxo lesion. |
| Keywords: | nmr; oxidative damage; 1h nmr; solution structure; aoxo · t alignment |
| Journal Title: | Magnetic Resonance in Chemistry |
| Volume: | 34 |
| Issue: | 13 |
| ISSN: | 0749-1581 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1996-12-01 |
| Start Page: | S23 |
| End Page: | S32 |
| Language: | English |
| PROVIDER: | scopus |
| DOI: | 10.1002/(SICI)1097-458X(199612)34:13<S23::AID-OMR16>3.0.CO;2-V |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
