Tri‐G‐Quadruplex: Controlled Assembly of a G‐Quadruplex Structure from Three G‐Rich Strands

Zhou, Jun; Bourdoncle, Anne; Rosu, Frédéric; Gabelica, Valérie; Mergny, Jean‐Louis

doi:10.1002/anie.201205390

Cited by 65 publications

(23 citation statements)

References 30 publications

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“…Stacks of G-quartets are stabilised by cations centrally coordinated to O6 of the guanines with stabilising preference for monovalent cations in the order K + > Na + > Li + (Figure 1A) [8]. G4s can be unimolecular or intermolecular and can adopt a wide diversity of topologies arising from different combinations of strand direction ( Figure 1D-F), as well as length and loop composition [9,10]. Structural studies using X-ray crystallography and NMR spectroscopy have provided detailed insights into the structure of DNA G4s primarily based on the human telomeric repeat ( Figure 1B,C) [11] or sequences derived from the promoter regions of certain human genes such as MYC or KIT [12,13].…”

Section: G4 Structurementioning

confidence: 99%

The Structure and Function of DNA G-Quadruplexes

Spiegel

Adhikari

Balasubramanian

2020

Trends in Chemistry

548

568

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Guanine-rich DNA sequences can fold into four-stranded, noncanonical secondary structures called G-quadruplexes (G4s). G4s were initially considered a structural curiosity, but recent evidence suggests their involvement in key genome functions such as transcription, replication, genome stability, and epigenetic regulation, together with numerous connections to cancer biology. Collectively, these advances have stimulated research probing G4 mechanisms and consequent opportunities for therapeutic intervention. Here, we provide a perspective on the structure and function of G4s with an emphasis on key molecules and methodological advances that enable the study of G4 structures in human cells. We also critically examine recent mechanistic insights into G4 biology and protein interaction partners and highlight opportunities for drug discovery. Beyond the DNA Double HelixA chemist's perspective on the function of a molecule, or a system of molecules, is typically led by a consideration of how molecular structure dictates function. The most widely recognised DNA structure is that of the classical DNA double helix [1], which defines a structural basis for the genetic code via defined base-pairing. Yet, it is evident that DNA is structurally dynamic and capable of adopting alternative secondary structures. One such class of DNA secondary structure is the four-stranded Gquadruplex (G4). Herein, we discuss some of the key scientific history that has shaped our understanding of this structural motif, its probable functions in biology, and major unanswered questions that remain to be solved.

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Section: G4 Structurementioning

confidence: 99%

The Structure and Function of DNA G-Quadruplexes

Spiegel

Adhikari

Balasubramanian

2020

Trends in Chemistry

548

568

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“…In the field of DNA G-quadruplexes, which are the best preserved in the gas phase, mass spectrometry is more and more routinely combined with in-solution structural and biophysics techniques to study NA folding or ligand binding. [152][153][154][155][156][157] This kind of application to solution phase problems however requires that the key structural elements are preserved or modified in a predictable way such that the gas phase structure keeps a memory of the initial structure in solution. A task lying ahead is to determine the range of other NA structures for which preservation is most likely, and in which conditions.…”

Section: Vi2 Opportunities and Challenges In Gas-phase Structural Bmentioning

confidence: 99%

Nucleic acid ion structures in the gas phase

Abi-Ghanem

Gabelica

2014

Phys. Chem. Chem. Phys.

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Nucleic acids are diverse polymeric macromolecules that are essential for all life forms. These biomolecules possess a functional three-dimensional structure under aqueous physiological conditions. Mass spectrometry-based approaches have on the other hand opened the possibility to gain structural information on nucleic acids from gas-phase measurements. To correlate gas-phase structural probing results with solution structures, it is therefore important to grasp the extent to which nucleic acid structures are preserved, or altered, when transferred from the solution to a fully anhydrous environment. We will review here experimental and theoretical approaches available to characterize the structure of nucleic acids in the gas phase (with a focus on oligonucleotides and higher-order structures), and will summarize the structural features of nucleic acids that can be preserved in the gas phase on the experiment time scale.

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“…For instance, it has been proposed that the quadruplex structure is regulated by sodium–potassium exchange (15). In addition to the strand polarity (parallel, antiparallel or mixed), glycosidic torsion angle ( syn or anti ) and the orientation of the loops (lateral, diagonal or both) (16), the G-quadruplex structures can also be differentiated by considering the stoichiometry of the strands into one (exclusively intramolecular structure) (5), two [for example, (3 + 1) type structure] (17), three (as we have described recently) (18) or four strands (19) (described in this report).…”

Section: Introductionmentioning

confidence: 99%

Controlling the stoichiometry and strand polarity of a tetramolecular G-quadruplex structure by using a DNA origami frame

Rajendran¹,

Endo²,

Hidaka³

et al. 2013

Nucleic Acids Research

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Guanine-rich oligonucleotides often show a strong tendency to form supramolecular architecture, the so-called G-quadruplex structure. Because of the biological significance, it is now considered to be one of the most important conformations of DNA. Here, we describe the direct visualization and single-molecule analysis of the formation of a tetramolecular G-quadruplex in KCl solution. The conformational changes were carried out by incorporating two duplex DNAs, with G–G mismatch repeats in the middle, inside a DNA origami frame and monitoring the topology change of the strands. In the absence of KCl, incorporated duplexes had no interaction and laid parallel to each other. Addition of KCl induced the formation of a G-quadruplex structure by stably binding the duplexes to each other in the middle. Such a quadruplex formation allowed the DNA synapsis without disturbing the duplex regions of the participating sequences, and resulted in an X-shaped structure that was monitored by atomic force microscopy. Further, the G-quadruplex formation in KCl solution and its disruption in KCl-free buffer were analyzed in real-time. The orientation of the G-quadruplex is often difficult to control and investigate using traditional biochemical methods. However, our method using DNA origami could successfully control the strand orientations, topology and stoichiometry of the G-quadruplex.

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Tri‐G‐Quadruplex: Controlled Assembly of a G‐Quadruplex Structure from Three G‐Rich Strands

Cited by 65 publications

References 30 publications

The Structure and Function of DNA G-Quadruplexes

The Structure and Function of DNA G-Quadruplexes

Nucleic acid ion structures in the gas phase

Controlling the stoichiometry and strand polarity of a tetramolecular G-quadruplex structure by using a DNA origami frame

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