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|Title:||Base pair mismatches and carcinogen-modified bases in DNA: An NMR study of A·C and A·O4meT pairing in dodecanucleotide duplexes||Authors:||Kalnik, M.W.
|Issue Date:||1988||Citation:||Kalnik, M.W.,Kouchakdjian, M.,Li, B.F.L.,Swann, P.F.,Patel, D.J. (1988). Base pair mismatches and carcinogen-modified bases in DNA: An NMR study of A·C and A·O4meT pairing in dodecanucleotide duplexes. Biochemistry 27 (1) : 100-108. ScholarBank@NUS Repository.||Abstract:||Structural features of A·C mismatches and A·O4meT pairs in the interior of oligodeoxynucleotide duplexes have been investigated by high-resolution two-dimensional proton NMR spectroscopy on the self-complementary d(C-G-C-A-A-G-C-T-C-G-C-G) duplex (designated A·C 12-mer) and the self-complementary d(C-G-C-A-A-G-C-T-O4meT-G-C-G) duplex (designated A·O4meT 12-mer) containing A·C and A·O4meT pairs at identical positions four base pairs in from either end of the duplex. Proton NMR shows that there are similar pH-dependent changes in the structure in the A·C 12-mer and A·O4meT 12-mer duplexes. Our studies have focused on the low-pH (pH 5.5) conformation where high-quality two-dimensional NOESY data sets were collected from the exchangeable and nonexchangeable protons in these duplexes. The spectral parameters for the A·C 12-mer and the A·O4meT 12-mer duplexes were very similar, indicating that they must have similar structures at this pH in aqueous solution. Both structures are right-handed double helices with all the bases adopting the normal anti configuration about the glycosidic bond. The same atoms are involved in hydrogen-bond pairing for the A·C mismatch and the A·O4meT pair, and these pairs have a similar spatial relationship to flanking base pairs. X-ray crystallography [Hunter, W. N., Brown, T., Anand, N. N., & Kennard, O. (1986) Nature (London) 320, 552-555] recently confirmed the wobble pairing structure for the A·C mismatch, which had previously been suggested from NMR studies on solutions of oligonucleotide duplexes [Patel, D. J., Kozlowski, S. A., Ikuta, S., & Itakura, K. (1984) Biochemistry 23, 3218-3226] and from theoretical calculations [Keepers, J. W., Schmidt, P., James, T. L., & Kollman, P. A. (1984) Biopolymers 23, 2901-2929]. The comparative NMR study on the A·C 12-mer and A·O4meT 12-mer duplexes demonstrates similar wobble pairing for the A·O4meT lesion. We can monitor the amino protons of A in the A·C mismatch and the A·O4meT pair in the low-pH spectra (pH 5.5-6.0), providing additional markers at the modification sites. Further, the distance-dependent NOE measurements establish that the OCH3 group of O4meT adopts a syn orientation with respect to N3 of the base and is directed toward the A on the partner strand in the A·O4meT pair. The lateral displacement of the bases in the wobble pairing allows the OCH3 group in the syn orientation to be accommodated in the helix. © 1988 American Chemical Society.||Source Title:||Biochemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/111799||ISSN:||00062960|
|Appears in Collections:||Staff Publications|
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