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Kinetics of double-chain reversals bridging contiguous quartets in tetramolecular quadruplexes.

Authors
  • Mergny, Jean-Louis
  • De Cian, Anne
  • Amrane, Samir
  • Webba da Silva, Mateus
Type
Published Article
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Publication Date
Jan 01, 2006
Volume
34
Issue
8
Pages
2386–2397
Identifiers
PMID: 16682446
Source
Medline
License
Unknown

Abstract

Repetitive 5'GGXGG DNA segments abound in, or near, regulatory regions of the genome and may form unusual structures called G-quadruplexes. Using NMR spectroscopy, we demonstrate that a family of 5'GCGGXGGY sequences adopts a folding topology containing double-chain reversals. The topology is composed of two bistranded quadruplex monomeric units linked by formation of G:C:G:C tetrads. We provide a complete thermodynamic and kinetic analysis of 13 different sequences using absorbance spectroscopy and DSC, and compare their kinetics with a canonical tetrameric parallel-stranded quadruplex formed by TG4T. We demonstrate large differences (up to 10(5)-fold) in the association constants of these quadruplexes depending on primary sequence; the fastest samples exhibiting association rate equal or higher than the canonical TG4T quadruplex. In contrast, all sequences studied here unfold at a lower temperature than this quadruplex. Some sequences have thermodynamic stability comparable to the canonical TG4T tetramolecular quadruplex, but with faster association and dissociation. Sequence effects on the dissociation processes are discussed in light of structural data.

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