Book of Abstracts: Albany 2003

category image Albany 2003
Conversation 13
Abstract Book
June 17-21 2003

23Na, 17O and 2H MRD Investigations of DNA Quadruplexes

Guanine quadruplexes are nucleic acid structures built around a core of three or more stacked G-tetrads, planar arrangements of four guanine bases linked by eight Hoogsteen hydrogen bonds and stabilized by a central monovalent cation, usually K+ or Na+ (1). These internal ions, positioned on the helix axis, coordinate the guanine O6 carbonyl oxygens. The ends of linear chromosomes, termed telomeres, contain repeats of guanine-rich sequences, that can form G-quadruplexes under appropriate conditions, and may play an important role in cellular processes like transcriptional regulation. Notwithstanding the growing number of X-ray and NMR-derived quadruplex structures, little is known about the internal ions.

Quadruplex structures delimit four grooves, at the floor of which ordered water molecules are often revealed by X-ray crystallography (2). As compared to B-DNA, quadruplexes appear to have a more rigid and strained backbone, which might give rise to longer water residence times in the grooves. Dimeric quadruplexes exhibit a pronounced polymorphism and tend to form more easily in the presence of K+ cations (3). Lateral loops and water molecules may block the entrance to the ion channel and affect the exchange dynamics of the internal ions.

Here, we report the first magnetic relaxation dispersion (MRD) study of the interaction of quadruplex DNA with water and ions. Using 23Na, 17O and 2H MRD, we focus on long-lived water molecules in the grooves and on the buried Na+ ions. Na+/K+ competition experiments have also been carried out. Results will be presented of our MRD studies of the two dimeric quadruplexes [d(G3T4G3)]2 and [d(G4T4G4)]2.

Karim Snoussi1
Bertil Halle2

Biophysical Chemistry
Lund University
P. O. Box 124
SE-22100 Lund, Sweden

References and Footnotes
  1. J. R. Williamson, Annu. Rev. Biophys. Biomol. Struct. 23, 703?730 (1994).
  2. M. P. Horvath and S. C. Schultz, J. Mol. Biol. 310, 367?377 (2001).
  3. P. Schultze, N. V. Hud, F. W. Smith and J. Feigon, Nucl. Acids Res. 27, 3018?3028 (1999).