Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of A.C and A.O4meT pairing in dodecanucleotide duplexes.

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 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 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.(ABSTRACT TRUNCATED AT 250 WORDS)