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doi:10.1016/j.bmc.2006.04.033 
Copyright © 2006 Published by Elsevier Ltd.
The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution
Received 7 April 2006;
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Abstract
The human telomeric sequence d[AGGG(TTAGGG)3] has been found to form different types of G-quadruplex structures. NMR revealed that in Na+ solution this 22 nucleotide (nt) sequence exhibits an antiparallel structure, whereas crystallographic studies in the presence of K+ showed a dramatically different parallel structure. The structure of this 22 nt sequence in the presence of K+ has drawn intense interest as the intracellular K+ concentration is greater than that of Na+. However, the question of the type of structure for the 22 nt telomeric sequence in K+ solution remains open. In this study, we substituted the Gs in the sequence with 8-bromoguanine and examined the resultant structures and thermal stabilities by circular dichroism (CD) spectroscopy. The results suggest that the 22 nt in K+ solution exists as a mixture of mixed-parallel/antiparallel and chair-type G-quadruplex. To date, the exact structure of human telomeric G-quadruplex in K+ solution is extremely controversial. The present study provides valuable information for understanding the discrepancies between the crystal and solution studies. We discuss the possible implications of the structure in understanding higher-order telomeric DNA structure and T-loop formation.
Graphical abstract
We substituted the Gs in the sequence with 8-bromoguanine and examined the resultant structures and thermal stabilities by circular dichroism (CD) spectroscopy. The results suggest that the 22 nt in K+ solution exists as a mixture of mixed-parallel/antiparallel and chair-type G-quadruplex.
Keywords: DNA structure; G-quadruplex; Modified nuclei acids; Telomere; Thermal stability
Article Outline
- 1. Introduction
- 2. Results and discussion
- 2.1. CD spectrum of 22 nt sequence in K+ solution
- 2.2. The mixed parallel/antiparallel structure
- 2.3. The chair-type structure
- 2.4. Possible biological implication
- 3. Materials and methods
- 3.1. Synthesis of oligonucleotides
- 3.2. CD measurements and analysis of CD melting profiles
- 3.3. Molecular modeling studies
- Acknowledgements
- References
