Human telomeric DNA: G-quadruplex, i-motif and Watson–Crick double helix

Human telomeric DNA composed of (TTAGGG/CCCTAA)(n) repeats may form a classical Watson–Crick double helix. Each individual strand is also prone to quadruplex formation: the G-rich strand may adopt a G-quadruplex conformation involving G-quartets whereas the C-rich strand may fold into an i-motif based on intercalated C·C(+) base pairs. Using an equimolar mixture of the telomeric oligonucleotides d[AGGG(TTAGGG)(3)] and d[(CCCTAA)(3)CCCT], we defined which structures existed and which would be the predominant species under a variety of experimental conditions. Under near-physiological conditions of pH, temperature and salt concentration, telomeric DNA was predominantly in a double-helix form. However, at lower pH values or higher temperatures, the G-quadruplex and/or the i-motif efficiently competed with the duplex. We also present kinetic and thermodynamic data for duplex association and for G-quadruplex/i-motif unfolding.