Thermodynamic characterization of human telomere quadruplex unfolding

R. Buscaglia, R. D. Gray, J. B. Chaires

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The 3′-terminal extensions of eukaryotic chromosomes are unique examples of functional single-stranded DNA. Human telomeres are constructed of the repeated DNA sequence 5′-d(TTAGGG). Four-repeats of human telomeric DNA have been characterized by high-resolution techniques to be capable of forming at least five distinct monomeric conformations. The predominant solution topology is influenced by solution conditions and the presence of 3′- or 5′-flanking residues. This study describes the unfolding mechanisms for human telomeric quadruplexes formed by eight sequence variants that form three unique antiparallel topologies in K+ solution. Thermal unfolding monitored by circular dichroism is analyzed by singular value decomposition to enumerate the number of significant spectral species required to model the unfolding process. Thermal denaturation of all quadruplexes studied is found to be best modeled by a four-state sequential mechanism with two populated intermediates. The thermal unfolding was also investigated in 50% (v/v) acetonitrile in which a parallel topology is favored. Under these dehydrating conditions, quadruplex thermal denaturation is best modeled by a three-state sequential unfolding mechanism with one populated intermediate. Dehydrated parallel quadruplexes demonstrate increased thermal stability. The spectral properties of the unfolding intermediate suggest that it is most likely a triple-helical structure. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1006-1018, 2013.

Original languageEnglish (US)
Pages (from-to)1006-1018
Number of pages13
JournalBiopolymers
Volume99
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • quadruplex
  • singular value decomposition
  • spectroscopy
  • telomere
  • unfolding

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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