SUNY at Albany
June 19-23, 2001
Stacked Watson-Crick Base Pairs
A series of DNA heptadecamers containing the DNA analogues of RNA E-like 5'-d(GXA)/(AYG)-5' motifs (X and Y are complementary T/A, A/T, C/G, or G/C paris) 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 unorthodox NOEs (nuclear Overhauser effect) that allow for well determination of an unusual zipper-like conformation; the potential canonical X:Y H-bonding is not present, and the central X/Y pairs are instead transformed into interstrand stacks that are bracketed by a pair of sheared G:A base pairs. These motifs are similar to the (GGA)2 motif possibly exist in the human centromeric (TGGAA)n tandem repeat sequence. Such motifs are only 5-8¢X C less stable than the (GGA)2 motif, which suggest that interstrand base stacking play a critical role in stabilizing unusual nucleic acid structures. This novel finding that canonical Watson-Crick G:C or A:T H-bonding pairs can be transformed into stacking pairs greatly increase the repertoire for unusual nucleic acid structural motifs.
Institute of Biochemistry,