i-Motif DNA: structural features and significance to cell biology

Assi, Hala Abou; Garavís, Miguel; González, Carlos; Damha, Masad J.

doi:10.1093/nar/gky735

Cited by 291 publications

(301 citation statements)

References 131 publications

(193 reference statements)

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“…Cytosine-rich regions have the ability to form af olded structure known as the i-motif.This DNAstructure consists of parallel-stranded duplexes held together through intercalated hemiprotonated CH + :C base pairs (Figure 7a,b). [55] As Ag I ions had successfully been applied to substitute aproton of ahydrogen bond within abase pair (see Figure 2 for selected examples), it seemed obvious to probe the formation of Ag I -modified i-motifs.I nterestingly,o pposing conclusions have been drawn from the data obtained during such experiments,including either the formation of an i-motif structure with C-Ag I -C pairs or the formation of nonintercalating duplexes bearing C-Ag I -C pairs. [56] Based on more recent experimental and computational investigations of contiguous Ag I -mediated homo base pairs,the formation of non-intercalating double-stranded helices with C-Ag I -C pairs appears to be more likely.…”

Section: Metal-mediated I-motif Structuresmentioning

confidence: 99%

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

2019

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The incorporation of metal ions into nucleic acids by means of metal‐mediated base pairs represents a promising and prominent strategy for the site‐specific decoration of these self‐assembling supramolecules with metal‐based functionality. Over the past 20 years, numerous nucleoside surrogates have been introduced in this respect, broadening the metal scope by providing perfectly tailored metal‐binding sites. More recently, artificial nucleosides derived from natural purine or pyrimidine bases have moved into the focus of AgI‐mediated base pairing, due to their expected compatibility with regular Watson–Crick base pairs. This minireview summarizes these advances in metal‐mediated base pairing but also includes further recent progress in the field. Moreover, it addresses other aspects of metal‐modified nucleic acids, highlighting an expansion of the concept to metal‐mediated base triples (in triple helices and three‐way junctions) and metal‐mediated base tetrads (in quadruplexes). For all types of metal‐modified nucleic acids, proposed or accomplished applications are briefly mentioned, too.

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Section: Metal-mediated I-motif Structuresmentioning

confidence: 99%

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

2019

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“…Nucleic acids are well known for their ability to form a wide range of higher‐order structures, a property that allows these molecules to fulfil a wide range of fascinating and important functions. In biology, the DNA double helix provides the means of information storage for the whole of life .…”

Section: Introductionmentioning

confidence: 99%

“…Nucleic acids are well known for their ability to form a wide range of higher-order structures, [1][2][3] a property that allows these molecules to fulfil a wide range of fascinating and important functions. In biology, the DNA double helix provides the specificity and affinity, but such ligands can also be engineered to do more than simply associate with G4 in a straightforward host-guest fashion.…”

Section: Introductionmentioning

confidence: 99%

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

2019

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G‐quadruplexes (G4) are four‐stranded structures formed from guanine‐rich oligonucleotides. Their defined 3D structures and polymorphic nature set them apart from classical nucleic acid morphology and suggest a range of potential applications in the development of functional materials. Meanwhile, the occurrence of G4 across the genomes of animals, plants and pathogens suggests roles for these structures in biology that may be exploited for therapeutic effect. Hundreds of G4 ligands are reported to bind these sequences with high specificity and affinity, but such ligands can also be engineered to do more than simply associate with G4 in a straightforward host‐guest fashion. Ligands have been developed that can switch G4 topology, direct the selective covalent modification of nucleic acid structures, or respond to external stimuli to permit spatiotemporal control of their activity. Herein we survey the main themes of such “value‐added” G4 ligands and consider the opportunities and challenges of their potential applications.

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“…In addition to the well-known Watson-Crick double helix, nucleic acids can form several non-canonical structures, which are likely involved in the regulation of gene expression. One of them is the i-motif (intercalated motif) structure [1][2][3][4], formed by cytosine-rich DNA sequences, wherein the strands are inter-connected by intercalated hemiprotonated C-H + -C base pairs (Figure 1). i-motif formation is pH-dependent, and the pH of mid-transition from i-motif to unfolded structure depends on the C-tract length.…”

Section: Introductionmentioning

confidence: 99%

Native Ion Mobility Mass Spectrometry: When Gas-Phase Ion Structures Depend on the Electrospray Charging Process

Khristenko

Amato

Livet

et al. 2019

J. Am. Soc. Mass Spectrom.

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Ion mobility spectrometry (IMS) has become popular to characterize biomolecule folding.Numerous studies have shown that proteins that are folded in solution remain folded in the gas phase, whereas proteins that are unfolded in solution adopt more extended conformations in the gas phase. Here, we discuss how general this tenet is. We studied single-stranded DNAs (human telomeric cytosine-rich sequences with CCCTAA repeats), which fold into an intercalated motif (i-motif) structure in a pH-dependent manner, thanks to the formation of C-H + -C base pairs. As i-motif formation is favored at low ionic strength, we could investigate the ESI-IMS-MS behavior of i-motif structures at pH ~5.5 over a wide range of ammonium acetate concentrations (15 mM to 100 mM). The control experiments consisted of either the same sequence at pH ~7.5, wherein the sequence is unfolded, or sequence variants that cannot form i-motifs (CTCTAA repeats). The surprising results came from the control experiments. We found that the ionic strength of the solution had a greater effect on the compactness of the gas-phase structures than the solution folding state. This means that electrosprayed ions keep a memory of the charging process, which is influenced by the electrolyte concentration. We discuss these results in light of the analyte partitioning between the droplet interior and droplet surface, which in turn influences the probability of being ionized via a charged residue-type pathway or a chain extrusion-type pathway.

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i-Motif DNA: structural features and significance to cell biology

Cited by 291 publications

References 131 publications

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

Native Ion Mobility Mass Spectrometry: When Gas-Phase Ion Structures Depend on the Electrospray Charging Process

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