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Nucleic Acids Research Advance Access first published online on September 25, 2007
This version published online on October 3, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm706
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© 2007 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

Structure of two intramolecular G-quadruplexes formed by natural human telomere sequences in K+ solution{dagger}

Anh Tuân Phan1,2,*, Vitaly Kuryavyi1, Kim Ngoc Luu1 and Dinshaw J. Patel1

1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA and 2Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637551, Singapore

*To whom correspondence should be addressed. Tel: +65 6514 1915; Fax: +65 6794 1325; Email: phantuan{at}ntu.edu.sg Correspondence may also be addressed to Dinshaw J. Patel. Tel: + 1 212 639 7207; Fax: + 1 212 717 3066; Email: pateld{at}mskcc.org The authors wish to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

Received July 7, 2007. Revised August 24, 2007. Accepted August 24, 2007.

Intramolecular G-quadruplexes formed by human telomere sequences are attractive anticancer targets. Recently, four-repeat human telomere sequences have been shown to form two different intramolecular (3 + 1) G-quadruplexes in K+ solution (Form 1 and Form 2). Here we report on the solution structures of both Form 1 and Form 2 adopted by natural human telomere sequences. Both structures contain the (3 + 1) G-tetrad core with one double-chain-reversal and two edgewise loops, but differ in the successive order of loop arrangements within the G-quadruplex scaffold. Our results provide the structural details at the two ends of the G-tetrad core in the context of natural sequences and information on different loop conformations. This structural information might be important for our understanding of telomere G-quadruplex structures and for anticancer drug design targeted to such scaffolds.

{dagger} Much of this work was presented at the First International Quadruplex DNA Meeting, Louisville, KY, USA; April 2007.


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