Kinetics and mechanism of K+- and Na+-induced folding of models of human telomeric DNA into G-quadruplex structures

Robert D Gray, Jonathan B Chaires

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Abstract / Description of output

Cation-induced folding into quadruplex structures for three model human telomeric oligonucleotides, d[AGGG(TTAGGG)(3)], d[TTGGG(TTAGGG)(3)A] and d[TTGGG(TTAGGG)(3)], was characterized by equilibrium titrations with KCl and NaCl and by multiwavelength stopped flow kinetics. Cation binding was cooperative with Hill coefficients of 1.5-2.2 in K(+) and 2.4-2.9 in Na(+) with half-saturation concentrations of 0.5-1 mM for K(+) and 4-13 mM for Na(+) depending on the oligonucleotide sequence. Oligonucleotide folding in 50 mM KCl at 25 degrees C consisted of single exponential processes with relaxation times tau of 20-60 ms depending on the sequence. In contrast, folding in100 mM NaCl consisted of three exponentials with tau-values of 40-85 ms, 250-950 ms and 1.5-10.5 s. The folding rate constants approached limiting values with increasing cation concentration; in addition, the rates of folding decreased with increasing temperature over the range 15-45 degrees C. Taken together, these results suggest that folding of G-rich oligonucleotides into quadruplex structures proceeds via kinetically significant intermediates. These intermediates may consist of antiparallel hairpins in rapid equilibrium with less ordered structures. The hairpins may subsequently form nascent G-quartets stabilized by H-bonding and cation binding followed by relatively slow strand rearrangements to form the final completely folded topologies. Fewer kinetic intermediates were evident with K(+) than Na(+), suggesting a simpler folding pathway in K(+) solutions.
Original languageEnglish
Pages (from-to)4191-203
Number of pages13
JournalNucleic Acids Research
Volume36
Issue number12
DOIs
Publication statusPublished - 2008

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