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Quadruplexes of human telomere DNA analogs designed to contain G:A:G:A,G:G:A:A,and A:A:A:A tetrads
Authors:Janos Sagi  Daniel Renčiuk  Martin Tomaško  Michaela Vorlíčková
Institution:1. Rimstone Laboratory, RLI, 29 Lancaster Way, Cheshire, CT 06410;2. Institute of Biophysics, Academy of Sciences of the Czech Republic, Laboratory of CD Spectroscopy of Nucleic Acids, Královopolská 135, CZ‐61265 Brno, Czech Republic
Abstract: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. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 880–886, 2010.
Keywords:human telomere quadruplex  adenine for guanine substitution  CD spectroscopy  thermal stability  thermodynamic parameters  DMS methylation
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