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Oxford University Press, Nucleic Acids Research, 8(34), p. 2386-2397, 2006

DOI: 10.1093/nar/gkl098

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

Journal article published in 2006 by Anne De Cian, Mateus Webba da Silva, Jean-Louis Mergny ORCID, Samir Amrane ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.