Formation of highly ordered multimers in G-quadruplexes

Biochemistry. 2014 Nov 18;53(45):7013-27. doi: 10.1021/bi500773c. Epub 2014 Nov 7.

Abstract

G-Rich DNA and RNA have a higher propensity to form G-quadruplex structures, but the presence of G-runs alone is not sufficient to prove that such sequences can form stable G-quadruplexes. While G-rich sequences are essential for G-quadruplex formation, not all G-rich sequences have the propensity to form G-quadruplex structures. In addition, monovalent metal ions, dehydrating agents, and loop sequences connecting the G-runs also play important roles in the topology of G-quadruplex folding. To date, no quantitative analysis of the CD spectra of G-quadruplexes in confrontation with the electrophoretic results has been performed. Therefore, in this study, we use information gained through the analysis of a series of well-known G-quadruplex-forming sequences to evaluate other less-studied sets of aptameric sequences. A simple and cost-effective methodology that can verify the formation of G-quadruplex motifs from oligomeric DNA sequences and a technique to determine the molecularity of these structures are also described. This methodology could be of great use in the prediction of G-quadruplex assembly, and the basic principles of our techniques can be extrapolated for any G-rich DNA sequences. This study also presents a model that can predict the multimerization of G-quadruplexes; the predictions offered by this model are shown to match the results obtained using circular dichroism.

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / genetics
  • Circular Dichroism / methods*
  • Electrophoresis, Gel, Two-Dimensional / methods
  • G-Quadruplexes*
  • Protein Multimerization* / physiology

Substances

  • Aptamers, Nucleotide