Concentration-Dependent Structural Transitions of Human Telomeric DNA Sequences

Abu-Ghazalah, Rashid M.; Rutledge, Steve; Lau, Lewis W.Y.; Dubins, David N.; Macgregor, Robert B.; Helmy, Amr S.

doi:10.1021/bi300689t

Cited by 29 publications

(44 citation statements)

References 52 publications

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“…No influence of solution structure was seen for strand concentrations up to 0.4–0.5 uM, although high strand concentration has been proposed to influence solution structure. 38 …”

Section: Discussionmentioning

confidence: 99%

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Thermodynamic characterization of human telomere quadruplex unfolding

2013

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The 3'-terminal extension of eukaryotic chromosomes are a unique example of functional single-stranded DNA. Human telomeres are constructed of the repeated DNA sequence 5'-d(TTAGGG). Four-repeats of human telomeric DNA have been characterized by high-resolution techniques to be capable of forming at least five distinct monomeric conformations. The predominant solution topology is influenced by solution conditions and the presence of 3'- or 5'-flanking residues. This study extends recently described sequential unfolding mechanisms for human telomeric quadruplexes to eight telomeric DNA sequences that form three unique topologies. Thermal unfolding monitored by circular dichroism is subjected to singular value decomposition to enumarate the number of significant spectral species required to model the unfolding process. Thermal denaturations are found to be best modeled by a four-state sequential mechanism with ΔGave = −8.8 kcal mol−1. The thermal unfolding was also investigated in 50% (v/v) acetonitrile. Under dehydrated conditions, quadruplex thermal denaturations are best modeled by a three-state sequential unfolding mechanism. Dehydrated quadruplexes demonstrate increased thermal stability with ΔGave = −12.7 kcal mol−1. A common spectral intermediate is shared amongst human telomere quadruplex thermal unfolding regardless of starting topology and hydration state. This unfolding intermediate was recently characterized as an ensemble of triple-helical structures for a 22-nt human telomeric quadruplex.

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“…No influence of solution structure was seen for strand concentrations up to 0.4–0.5 uM, although high strand concentration has been proposed to influence solution structure. 38 …”

Section: Discussionmentioning

confidence: 99%

“…Diluted NMR samples gave CD spectra matching low concentration samples, indicating the high concentration used did not influence conformation. 38 …”

Section: Methodsmentioning

confidence: 99%

Thermodynamic characterization of human telomere quadruplex unfolding

2013

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“…[1][2][3][4][5][6][7][8][9][10][11] Human telomeres containing tandem repeats of sequence d(TTAGGG) at their extreme 3 0 -end are the complexes of DNA and proteins located at the ends of the chromosome, which play important roles in protecting chromosomes from fusion and degradation. 17,18 Until now, numerous methods have been used to analyze the structure of the human telomeric G-quadruplex in vitro, such as high-resolution solution state NMR, 5,[8][9][10]19 single crystal diffraction, 20 molecular dynamics (MD) simulations, [21][22][23] circular dichroism (CD), 7,22,[24][25][26] fluorescence, 7,27 differential scanning calorimetry (DSC), 28,29 mass spectrometry, 30,31 photon correlation spectroscopy, 32 atomic force microscopy (AFM), [33][34][35] analytical ultracentrifugation (AUC) 7,36-39 and so on. 17,18 Until now, numerous methods have been used to analyze the structure of the human telomeric G-quadruplex in vitro, such as high-resolution solution state NMR, 5,[8][9][10]19 single crystal diffraction, 20 molecular dynamics (MD) simulations, [21]…”

Section: Introductionmentioning

confidence: 99%

“…The structure and stability of the human telomeric G-quadruplex are determined by the concentration 24 and sequence 9,21 of DNA and the nature and concentration of cations in solutions, [7][8][9]25,40,41 ligands 26,42 and cosolvents. 10,30 Among these conditions, cations play an important role.…”

Section: Introductionmentioning

confidence: 99%

The effects of monovalent metal ions on the conformation of human telomere DNA using analytical ultracentrifugation

Gao

2016

Soft Matter

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A human telomere DNA segment (HT-DNA) can fold into a G-quadruplex in the presence of some monovalent cations. These cations can interact with the phosphate groups of the DNA segment and/or with the O6 oxygen atom of guanines, which are called non-specific interactions and specific interactions, respectively. However, until now how these two interactions affect the structure of HT-DNA has not been well understood. In this study, a combination of analytical ultracentrifugation (AUC) and circular dichroism (CD) was used to explore the effects of these two interactions on the structure of a 22-mer single-stranded DNA with a sequence of 5'-AGGG(TTAGGG)3-3'. The results showed that the standard sedimentation coefficient (s20,w) of HT-DNA starts to increase when the concentration of potassium ions (CK(+)) is higher than 10.0 µM due to the formation of a G-quadruplex through specific interactions. Whereas, for a control DNA, a higher CK(+) value of 1.0 mM was needed for increasing s20,w due to non-specific interactions. Moreover, potassium ions could promote the formation of the G-quadruplex much more easily than lithium, sodium and cesium ions, presumably due to its appropriate size in the dehydrated state and easier dehydration. The molar mass of DNA at different cation concentrations was nearly a constant and close to the theoretical value of the molar mass of monomeric HT-DNA, indicating that what we observed is the structural change of individual DNA chains.

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“…If we assume that at low (micromolar) concentrations, both sodium and potassium structures of TQ23 have the same (3+1) topology, then it would be difficult to explain remarkably altered mode of interaction of these conformers with ZnP1 by local differences in the tetrads stacking or tensions in the loops brought about by sodium ions. On the other hand, several studies have demonstrated that a high oligonucleotide concentration coupled with prolonged incubation of the telomeric G-DNA may cause a tremendous change of the initial structure (32–34). We believe that the diverse solution conditions of low (this study) and high (NMR) oligonucleotide concentrations as well as applied renaturation procedures may cause the inconsistency.…”

Section: Discussionmentioning

confidence: 99%

Light-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin

et al. 2016

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Structure-specific ligands are convenient tools for the recognition, targeting or probing of non-canonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (ZnP1) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)3) at submicromolar concentrations without any detectible disturbance of the particular fold. Among different folds, potassium (3+1) hybrid G4-structure. reveal the highest affinity to ZnP1. The pattern of guanine oxidation is specific for each telomeric DNA conformation and may serve as an additional tool for probing the G4 topology. The potassium (3+1) and parallel G4 conformations are more susceptible to light-induced oxidation than the sodium G4 conformation or double helix of the telomeric DNA. The major products of the guanine modifications are spiroiminodihydantoin (Sp) and 8-oxoguanine (8-oxoG). ZnP1-induced oxidation of guanines results in the structural rearrangement of parallel and (3+1) G4 conformations yielding an antiparallel-like G4 conformation. The mechanism of the observed light-induced conformational changes is discussed.

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Concentration-Dependent Structural Transitions of Human Telomeric DNA Sequences

Cited by 29 publications

References 52 publications

Thermodynamic characterization of human telomere quadruplex unfolding

Thermodynamic characterization of human telomere quadruplex unfolding

The effects of monovalent metal ions on the conformation of human telomere DNA using analytical ultracentrifugation

Light-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin

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