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Nucleic Acids Research Advance Access published online on June 18, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm316
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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

Intramolecular DNA quadruplexes with different arrangements of short and long loops

Phillip A. Rachwal1, I. Stuart Findlow1, Joern M. Werner1, Tom Brown2 and Keith R. Fox1,*

1School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK and 2School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK

*To whom correspondence should be addressed. Tel: +44 23 8059 4374; Fax: +44 23 8059 4459; Email: k.r.fox{at}soton.ac.uk

Received March 10, 2007. Accepted April 13, 2007.

We have examined the folding, stability and kinetics of intramolecular quadruplexes formed by DNA sequences containing four G3 tracts separated by either single T or T4 loops. All these sequences fold to form intramolecular quadruplexes and 1D-NMR spectra suggest that they each adopt unique structures (with the exception of the sequence with all three loops containing T4, which is polymorphic). The stability increases with the number of single T loops, though the arrangement of different length loops has little effect. In the presence of potassium ions, the oligonucleotides that contain at least one single T loop exhibit similar CD spectra, which are indicative of a parallel topology. In contrast, when all three loops are substituted with T4 the CD spectrum is typical of an antiparallel arrangement. In the presence of sodium ions, the sequences with two and three single T loops also adopt a parallel folded structure. Kinetic studies on the complexes with one or two T4 loops in the presence of potassium ions reveal that sequences with longer loops display slower folding rates.


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