Kinetics of tetramolecular quadruplexes.
The melting of tetramolecular DNA or RNA quadruplexes is kinetically irreversible. However, rather than being a hindrance, this kinetic inertia allows us to study association and dissociation processes independently. From a kinetic point of view, the association reaction is fourth order in monomer and the dissociation first order in quadruplex. The association rate constant k (on), expressed in M(-3) x s(-1) decreases with increasing temperature, reflecting a negative activation energy (E (on)) for the sequences presented here. Association is favored by an increase in monocation concentration. The first-order dissociation process is temperature dependent, with a very positive activation energy E (off), but nearly ionic strength independent. General rules may be drawn up for various DNA and RNA sequence motifs, involving 3-6 consecutive guanines and 0-5 protruding bases. RNA quadruplexes are more stable than their DNA counterparts as a result of both faster association and slower dissociation. In most cases, no dissociation is found for G-tracts of 5 guanines or more in sodium, 4 guanines or more in potassium. The data collected here allow us to predict the amount of time required for 50% (or 90%) quadruplex formation as a function of strand sequence and concentration, temperature and ionic strength.
Mergny
Jean-Louis
JL
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle USM503 INSERM U565, CNRS UMR 5153, 43 rue Cuvier, 75231 Paris Cedex 05, France. mergny@vnumail.com
De Cian
Anne
A
Ghelab
Amar
A
Saccà
Barbara
B
Lacroix
Laurent
L
D001483:Base Sequence; D002021:Buffers; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D007700:Kinetics; D009691:Nucleic Acid Denaturation; D009695:Nucleic Acid Renaturation; D009994:Osmolar Concentration; D012313:RNA / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
D002021:Buffers; D006147:Guanine; D012313:RNA; D004247:DNA