SUNY at Albany
June 19-23, 2001
The Solution Structure of a DNA Double Helix Incorporating a Track of Four Different Non-Canonical Base Pairs.
A series of DNA 21-mers containing a variety of 4 x 4 internal loop sequence 5'-CAAG-3'/3'-ACGT-5' were studied using nuclear magnetic resonance (NMR) methodology and distance geometry (DG) /molecular dynamics (MD) approaches. Such oligomers reveal excellent resolution in the NMR spectra and exhibit many unusual NOEs (nuclear Overhauser effect) that allow for the well characterization of a DNA hairpin incorporating a track of four different non-canonical base pairs in the stem, which include a wobble C:A base pair, a sheared A:C base pair, a sheared A:G base pair, and a wobble G:T base pair. Excellent base stacking is observed throughout the four consecutive mismatches, which explain why it exhibits a decent UV-melting temperature at 55 C even five out of ten base pairs in the stem region are mismatched. Most backbone torsion angles remain unchanged, except for the zeta torsion angle adjustment from gauche- to trans to incorporate a cross-strand base stack in the tandem sheared base-paired region. The four consecutive non-canonical base pairs observed in this manuscript increase the limited repertoire of irregular DNA folds known to date.
Ko-Hsin Chin & Shan-Ho Chou*
Institute of Biochemistry
National Chung-Hsing University