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

We examined the stability and kinetics of folding of the Oxytricha telomeric repeat sequence (G,T,),. 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 degrees 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 degrees C in the presence of 50 mM K+. The association reaction has a half-life of a few seconds at 37 degrees C, but becomes slower at elevated temperatures consistent with the suggestion that association occurs by a nucleation-zipper mechanism.