Quadruplexes of human telomere DNA analogs designed to contain G:A:G:A, G:G:A:A, and A:A:A:A tetrads.
Replacement of two to four guanines by adenines in the human telomere DNA repeat dG3(TTAG3)3 did not hinder the formation of quadruplexes if the substitutions took place in the terminal tetrad bridged by the diagonal loop of the intramolecular antiparallel three-tetrad scaffold, as proved by CD and PAGE in both Na+ and K+ solutions. Thermodynamic data showed that, in Na+ solution, the dG3(TTAG3)3 quadruplex was destabilized, the least by the two G:A:G:A tetrads, the most by the G:G:A:A tetrad in which the adenosines replaced syn-guanosines. In physiological K+ solution, the highest destabilization was caused by the 4A tetrad. In K+, only the unmodified dG3(TTAG3)3 quadruplex rearranged into a K+-dependent quadruplex form, none of the multiple adenine-modified structures did so. This may imply biological consequences for nonrepaired A-for-G mutations.
Sagi
Janos
J
Rimstone Laboratory, RLI, 29 Lancaster Way, Cheshire, CT 06410, USA.
Renciuk
Daniel
D
Tomasko
Martin
M
Vorlícková
Michaela
M
D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D054856:G-Quadruplexes; D006801:Humans; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D011188:Potassium; D012964:Sodium; D012996:Solutions; D016615:Telomere / Q000737:chemistry* / Q000235:genetics*; D013696:Temperature
D012996:Solutions; D004247:DNA; D012964:Sodium; D011188:Potassium; D004121:Dimethyl Sulfoxide