Arrangements of human telomere DNA quadruplex in physiologically relevant K⁺ solutions

• Published in: Nucleic acids research Vol. 37; no. 19; pp. 6625 - 6634
• Main Authors: Renčiuk, D, Kejnovská, I, Školáková, P, Bednářová, K, Motlová, J, Vorlíčková, M
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.2009
• Subjects: DNA - chemistry; Ethanol - pharmacology; G-Quadruplexes; Humans; Potassium - chemistry; Sodium - chemistry; Structural Biology; Telomere - chemistry
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkp701

The arrangement of the human telomeric quadruplex in physiologically relevant conditions has not yet been unambiguously determined. Our spectroscopic results suggest that the core quadruplex sequence G3(TTAG3)3 forms an antiparallel quadruplex of the same basket type in solution containing either K+ or Na+ ions. Analogous sequences extended by flanking nucleotides form a mixture of the antiparallel and hybrid (3 + 1) quadruplexes in K+-containing solutions. We, however, show that long telomeric DNA behaves in the same way as the basic G3(TTAG3)3 motif. Both G3(TTAG3)3 and long telomeric DNA are also able to adopt the (3 + 1) quadruplex structure: Molecular crowding conditions, simulated here by ethanol, induced a slow transition of the K+-stabilized quadruplex into the hybrid quadruplex structure and then into a parallel quadruplex arrangement at increased temperatures. Most importantly, we demonstrate that the same transitions can be induced even in aqueous, K+-containing solution by increasing the DNA concentration. This is why distinct quadruplex structures were detected for AG3(TTAG3)3 by X-ray, nuclear magnetic resonance and circular dichrosim spectroscopy: Depending on DNA concentration, the human telomeric DNA can adopt the antiparallel quadruplex, the (3 + 1) structure, or the parallel quadruplex in physiologically relevant concentrations of K+ ions.