Quadruplexes of human telomere DNA analogs designed to contain G:A:G:A,G:G:A:A,and A:A:A:A tetrads |
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Authors: | Janos Sagi Daniel Renčiuk Martin Tomaško Michaela Vorlíčková |
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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 |
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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. |
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Keywords: | human telomere quadruplex adenine for guanine substitution CD spectroscopy thermal stability thermodynamic parameters DMS methylation |
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