Tertiary DNA structure in the single-stranded hTERT promoter fragment unfolds and refolds by parallel pathways via cooperative or sequential events

Zhongbo Yu, Vanessa Gaerig, Yunxi Cui, Hyunjin Kang, Vijay Gokhale, Yuan Zhao, Laurence Hurley, Hanbin Mao

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The discovery of G-quadruplexes and other DNA secondary elements has increased the structural diversity of DNA well beyond the ubiquitous double helix. However, it remains to be determined whether tertiary interactions can take place in a DNA complex that contains more than one secondary structure. Using a new data analysis strategy that exploits the hysteresis region between the mechanical unfolding and refolding traces obtained by a laser-tweezers instrument, we now provide the first convincing kinetic and thermodynamic evidence that a higher order interaction takes place between a hairpin and a G-quadruplex in a single-stranded DNA fragment that is found in the promoter region of human telomerase. During the hierarchical unfolding or refolding of the DNA complex, a 15-nucleotide hairpin serves as a common species among three intermediates. Moreover, either a mutant that prevents this hairpin formation or the addition of a DNA fragment complementary to the hairpin destroys the cooperative kinetic events by removing the tertiary interaction mediated by the hairpin. The coexistence of the sequential and the cooperative refolding events provides direct evidence for a unifying kinetic partition mechanism previously observed only in large proteins and complex RNA structures. Not only does this result rationalize the current controversial observations for the long-range interaction in complex single-stranded DNA structures, but also this unexpected complexity in a promoter element provides additional justification for the biological function of these structures in cells.

Original languageEnglish (US)
Pages (from-to)5157-5164
Number of pages8
JournalJournal of the American Chemical Society
Volume134
Issue number11
DOIs
StatePublished - Mar 21 2012

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G-Quadruplexes
DNA
Single-Stranded DNA
Optical Tweezers
Telomerase
Kinetics
Thermodynamics
Genetic Promoter Regions
Nucleotides
Complementary DNA
RNA
Hysteresis
Proteins
Lasers

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Tertiary DNA structure in the single-stranded hTERT promoter fragment unfolds and refolds by parallel pathways via cooperative or sequential events. / Yu, Zhongbo; Gaerig, Vanessa; Cui, Yunxi; Kang, Hyunjin; Gokhale, Vijay; Zhao, Yuan; Hurley, Laurence; Mao, Hanbin.

In: Journal of the American Chemical Society, Vol. 134, No. 11, 21.03.2012, p. 5157-5164.

Research output: Contribution to journalArticle

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AU - Yu, Zhongbo

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AU - Kang, Hyunjin

AU - Gokhale, Vijay

AU - Zhao, Yuan

AU - Hurley, Laurence

AU - Mao, Hanbin

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