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Nucleic Acids Research Advance Access originally published online on October 12, 2006
Nucleic Acids Research 2006 34(19):5715-5719; doi:10.1093/nar/gkl726
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Nucleic Acids Research, 2006, Vol. 34, No. 19 5715-5719
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Structural Biology

Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution

Anh Tuân Phan*, Kim Ngoc Luu and Dinshaw J. Patel*

Structural Biology Program, Memorial Sloan-Kettering Cancer Center New York, NY 10021, USA

*To whom correspondence should be addressed. Tel: +65 6514 1915; Fax: +65 6794 1325; Email: phantuan{at}ntu.edu.sg

Received August 1, 2006. Revised September 18, 2006. Accepted September 19, 2006.

Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are promising anticancer targets. Here we show that four-repeat human telomeric DNA sequences can adopt two different intramolecular G-quadruplex folds in K+ solution. The two structures contain the (3+1) G-tetrad core, in which three G-tracts are oriented in one direction and the fourth in the opposite direction, with one double-chain-reversal and two edgewise loops, but involve different loop arrangements. This result indicates the robustness of the (3+1) core G-quadruplex topology, thereby suggesting it as an important platform for structure-based drug design. Our data also support the view that multiple human telomeric G-quadruplex conformations coexist in K+ solution. Furthermore, even small changes to flanking sequences can perturb the equilibrium between different coexisting G-quadruplex forms.

*Correspondence may also be addressed to Dinshaw J. Patel at: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, Box 557, 1275 York Avenue, New York, NY 10021, USA. Tel: +1 212 639 7207; Fax: +1 212 717 3066; Email: pateld{at}mskcc.org

Present address: Anh Tuân Phan, Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, SBS B3n-16, Singapore 637551


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