Polyelectrolyte Effects in G-Quadruplexes

Kim, Byul; Shek, Yuen Lai; Chalikian, Tigran V.

doi:10.1016/j.bpj.2013.11.437

Cited by 3 publications

(9 citation statements)

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“…Results of our previous studies suggest that counterion condensation may slightly increase the stability of a G-quadruplex, may not have any sizable impact on it, or may significantly destabilize it. 21,22 The K + -stabilized parallel G-quadruplex formed by the modified MYC22-G14T/G23T sequence from the promoter region of the human c-MYC oncogene is structurally and functionally similar to the Pu22-T12T13 G-quadruplex studied here. The MYC22-G14T/G23T G-quadruplex preformed in the atmosphere of K + ions is strongly destabilized in the presence of Cs + and TMA + cations.…”

Section: Discussionmentioning

confidence: 96%

“…21,22 Counterion condensation (the polyelectrolyte effect) has been found to dramatically decrease the thermal stability, T M , of the parallel G-quadruplex formed by a modified DNA sequence from the promoter region of the c-MYC oncogene. 22 Moreover, under some conditions, an increase in the concentration of Cs + ions in the solution of the K + -stabilized c-MYC G-quadruplex brings about its complete unfolding to the coil conformation.…”

Section: Introductionmentioning

confidence: 99%

“…12,17−20 In contrast to other ordered DNA structures, G-quadruplexes are subject to both specific and nonspecific ion binding. 12,21,22 The specific binding is due to metal ions coordinated inside the central cavity to the O6 oxygens of guanine bases, while the nonspecific binding involves external condensation of counterions around the phosphate groups. 12 In two recent publications, we have developed an experimental approach that permits one to discriminate between the contributions of specific and nonspecific cation binding to Gquadruplex stability.…”

Section: Introductionmentioning

confidence: 99%

“…12 In two recent publications, we have developed an experimental approach that permits one to discriminate between the contributions of specific and nonspecific cation binding to Gquadruplex stability. 21,22 In this approach, the thermal stability, T M , of a preformed G-quadruplex is measured as a function of the concentration of stabilizing and nonstabilizing monovalent cations. The stabilizing ions are the cations that support Gquadruplex formation by penetrating into the central cavity and forming coordination bonds with the N6 oxygens of the guanines.…”

Section: Introductionmentioning

confidence: 99%

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Ionic Effects on VEGF G-Quadruplex Stability

et al. 2016

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In a potassium solution, a modified 22-meric DNA sequence Pu22-T12T13 from a region proximal to the transcription initiation site of the human VEGF gene adopts a single parallel-stranded G-quadruplex conformation with a 1:4:1 loop-size arrangement. We measured the thermal stability, TM, of the K(+)-stabilized Pu22-T12T13 G-quadruplex as a function of stabilizing K(+) ions and nonstabilizing Cs(+) and TMA(+) ions. The thermal stability, TM, of the Pu22-T12T13 G-quadruplex increases with the concentration of the stabilizing potassium ions, while it sharply decreases upon the addition of the nonstabilizing cations. We interpret these results as underscoring the opposing effects of internal binding and counterion condensation on the stability of the Pu22-T12T13 G-quadruplex. While centrally bound ions stabilize the G-quadruplex conformation, counterion condensation destabilizes it, favoring the coil conformation. From the initial slopes of the dependences of TM on the concentration of Cs(+) and TMA(+) cations, we estimate that the deleterious effect of counterion condensation stems from roughly one extra counterion associated with the coil relative to the G-quadruplex state of Pu22-T12T13. The reduced accumulation of counterions around the G-quadruplex state of Pu22-T12T13 relative to its coil state is due to the low surface charge density of the G-quadruplex reflecting its structural characteristics. On the basis of the analysis of our data along with the results of a previous study, we propose that the differential effect of internally (stabilizing) and externally (destabilizing) bound cations may be a general feature of parallel intramolecular G-quadruplexes.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ionic Effects on VEGF G-Quadruplex Stability

et al. 2016

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“…Considering that G quadru plexes are formed due to association of four poly(oligo)anions, electrostatic interactions are their main stabilizing factor. However, the ions concentrated around the G quadruplex helix that neutralize the charges of phosphate groups in the sugar phosphate backbone contribute only slightly to G4 formation [28]. Unlike other types of structured nucleic acids, G4 specif ically bind (coordinate) ions of mono and bivalent met als within the highly electronegative central channel along the axis of the G4 stem [29]; the cations lose their hydration shell in the process.…”

Section: Structural Features Of Nucleic Acid G Quadruplexes and Factomentioning

confidence: 99%

Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

Dolinnaya

Ogloblina²,

Yakubovskaya³

2016

Biochemistry Moscow

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G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA-RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.

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Volumetric Properties of Four-Stranded DNA Structures

Chalikian

Macgregor

2021

Biology

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Four-stranded non-canonical DNA structures including G-quadruplexes and i-motifs have been found in the genome and are thought to be involved in regulation of biological function. These structures have been implicated in telomere biology, genomic instability, and regulation of transcription and translation events. To gain an understanding of the molecular determinants underlying the biological role of four-stranded DNA structures, their biophysical properties have been extensively studied. The limited libraries on volume, expansibility, and compressibility accumulated to date have begun to provide insights into the molecular origins of helix-to-coil and helix-to-helix conformational transitions involving four-stranded DNA structures. In this article, we review the recent progress in volumetric investigations of G-quadruplexes and i-motifs, emphasizing how such data can be used to characterize intra-and intermolecular interactions, including solvation. We describe how volumetric data can be interpreted at the molecular level to yield a better understanding of the role that solute–solvent interactions play in modulating the stability and recognition events of nucleic acids. Taken together, volumetric studies facilitate unveiling the molecular determinants of biological events involving biopolymers, including G-quadruplexes and i-motifs, by providing one more piece to the thermodynamic puzzle describing the energetics of cellular processes in vitro and, by extension, in vivo.

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Polyelectrolyte Effects in G-Quadruplexes

Cited by 3 publications

References 0 publications

Ionic Effects on VEGF G-Quadruplex Stability

Ionic Effects on VEGF G-Quadruplex Stability

Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

Volumetric Properties of Four-Stranded DNA Structures

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