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Nucleic Acids Research, 2002, Vol. 30, No. 21 4618-4625
© 2002 Oxford University Press

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

Anh Tuân Phan* and Jean-Louis Mergny1

Groupe de Biophysique du Laboratoire de Physique de la Matière Condensée, CNRS UMR 7643, Ecole Polytechnique, 91128 Palaiseau, France and 1 Laboratoire de Biophysique, Muséum National d’Histoire Naturelle, INSERM U565, CNRS UMR 8646, 75005 Paris, France

*To whom correspondence should be addressed at present address: Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, Box 557, 1275 York Avenue, New York, NY 10021, USA. Tel: +1 212 639 7225; Fax: +1 212 717 3066; Email: phantuan{at}sbnmr1.mskcc.org

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)3CCCT], 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.


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