Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, CZ-612 65 Brno, Czech Republic.
Biochem Biophys Res Commun. 2010 Aug 20;399(2):203-8. doi: 10.1016/j.bbrc.2010.07.055. Epub 2010 Jul 17.
This study was performed to evaluate how the loss of a guanine base affects the structure and stability of the three-tetrad G-quadruplex of 5'-dG(3)(TTAG(3))(3), the basic quadruplex-forming unit of the human telomere DNA. None of the 12 possible abasic sites hindered the formation of quadruplexes, but all reduced the thermodynamic stability of the parent quadruplex in both NaCl and KCl. The base loss did not change the Na(+)-stabilized intramolecular antiparallel architecture, based on CD spectra, but held up the conformational change induced in dG(3)(TTAG(3))(3) in physiological concentration of KCl. The reduced stability and the inhibited conformational transitions observed here in vitro for the first time may predict that unrepaired abasic sites in G-quadruplexes could lead to changes in the chromosome's terminal protection in vivo.
本研究旨在评估鸟嘌呤碱基的缺失如何影响 5'-dG(3)(TTAG(3))(3)三串联 G-四链体的结构和稳定性,5'-dG(3)(TTAG(3))(3)是人类端粒 DNA 的基本四链体形成单位。12 个可能的无碱基位点都没有阻碍四链体的形成,但在 NaCl 和 KCl 中,所有位点都降低了母体四链体的热力学稳定性。基于 CD 光谱,碱基缺失并未改变 Na(+)-稳定的分子内反平行结构,但在生理浓度的 KCl 中阻碍了 dG(3)(TTAG(3))(3)诱导的构象变化。这里首次在体外观察到稳定性降低和构象转变受到抑制,这可能预示着 G-四链体中未修复的无碱基位点可能导致体内染色体末端保护的改变。