GC ends control topology of DNA G-quadruplexes and their cation-dependent assembly

GCn and GCnCG, where n = (G(2)AG(4)AG(2)), fold into well-defined, dimeric G-quadruplexes with unprecedented folding topologies in the presence of Na(+) ions as revealed by nuclear magnetic resonance spectroscopy. Both G-quadruplexes exhibit unique combination of structural elements among which are two G-quartets, A(GGGG)A hexad and GCGC-quartet. Detailed structural characterization uncovered the crucial role of 5′-GC ends in formation of GCn and GCnCG G-quadruplexes. Folding in the presence of (15)NH(4)(+) and K(+) ions leads to 3′–3′ stacking of terminal G-quartets of GCn G-quadruplexes, while 3′-GC overhangs in GCnCG prevent dimerization. Results of the present study expand repertoire of possible G-quadruplex structures. This knowledge will be useful in DNA sequence design for nanotechnological applications that may require specific folding topology and multimerization properties.