Stacked Watson-Crick Base Pairs

Ko-Hsin Chin & Shan-Ho Chou*

Institute of Biochemistry

National Chung-Hsing University, Taichung, 40227, Taiwan


A series of DNA heptadecamers containing the DNA analogues of RNA E-like 5’-d(GXA)/(AYG)-5’ motifs (X and Y is complementary T/A, A/T, C/G, or G/C pair) were studied using nuclear magnetic resonance (NMR) methodology and distance geometry (DG) /molecular dynamics (MD) approaches. Such oligomers reveal excellent resolution in NMR spectra and exhibit many unusual NOEs (nuclear Overhauser effect) that allow for well characterization of an unusual zipper-like conformation with stacked Watson-Crick base pairs; the potential canonical X·Y H-bonding is not present, and the central X/Y pairs are transformed instead into inter-strand stacks that are bracketed by sheared G·A base pairs. Such phenomenal structural change is brought about mainly through two backbone torsional angle adjustments, i.e. d from C2’-endo to C3’-endo for the sugar puckers of unpaired residues and g from gauche+ to trans for the following 3’-adenosines. Such motifs are analogous to the previously studied (GGA)2 motif presumably present in the human centromeric (TGGAA)n tandem repeat sequence. The novel zipper-like motifs are only 4 – 7 °C less stable than the (GGA)2 motif, suggesting that inter-strand base stacking plays an important role in stabilizing unusual nucleic acid structures. The discovery that canonical Watson-Crick G·C or A·T hydrogen-bonded pairs can be transformed into stacking pairs greatly increase the repertoire for unusual nucleic acid structural motifs.