Exceptionally slow kinetics of the intramolecular quadruplex formed by the Oxytricha telomeric repeat

Abstract

We examined the stability and kinetics of folding of the Oxytricha telomeric repeat sequence (G₄T₄)₄. Fluorescence melting experiments show that this intramolecular quadruplex, which is more stable in potassium- than sodium-containing buffers, shows considerable hysteresis between the melting and annealing profiles, even when heated at a rate of 0.05 °C min⁻¹. Quantitative analysis of this hysteresis, together with temperature-jump relaxation experiments show that the dissociation is exceptionally slow with a half-life of about 10 years at 37 °C in the presence of 50 mM K⁺. The association reaction has a half-life of a few seconds at 37 °C, but becomes slower at elevated temperatures consistent with the suggestion that association occurs by a nucleation-zipper mechanism.