The Effect of DNA Sequence Directionality on G-Quadruplex Folding

Sequence inversion in G-rich DNA from 5'-> 3' to 3'-> 5' exerts a substantial effect on the number of structures formed, while the type of G-quadruplex fold is in fact determined by the presence of K+ or Na+ ions. The melting temperatures of G-quadruplexes adopted by oligonucleotides with sequences in the 5'-> 3' direction are higher than those of their 3'-> 5' counterparts with both KCl and NaCl. CD, UV, and NMR spectroscopy demonstrates the importance of primary sequence for the structural diversity of G-quadruplexes. The changes introduced by mere sequence reversal of the G-rich DNA segment have a substantial impact on the polymorphic nature of the resulting G-quadruplexes and their potential physiological roles. The insights resulting from this study should enable extension of the empirical rules for the prediction of G-quadruplex topology.