scholarly journals Probing Human Telomeric DNA and RNA Topology and Ligand Binding in a Cellular Model by Using Responsive Fluorescent Nucleoside Probes

ChemBioChem ◽  
2017 ◽  
Vol 18 (16) ◽  
pp. 1604-1615 ◽  
Author(s):  
Sudeshna Manna ◽  
Cornelia H. Panse ◽  
Vyankat A. Sontakke ◽  
Sarangamath Sangamesh ◽  
Seergazhi G. Srivatsan
Keyword(s):  
Ligand Binding ◽  
Cellular Model ◽  
Telomeric Dna ◽  
Dna And Rna ◽  
Fluorescent Nucleoside

scholarly journals Mass spectrometric studies on effects of counter ions of TMPyP4 on binding to human telomeric DNA and RNA G-quadruplexes

2014 ◽  
Vol 406 (22) ◽  
pp. 5455-5463 ◽  
Author(s):  
Li-Ping Bai ◽  
Jie Liu ◽  
Li Han ◽  
Hing-Man Ho ◽  
Renxiao Wang ◽  
...  
Keyword(s):  
Mass Spectrometric ◽  
Telomeric Dna ◽  
Dna And Rna ◽  
Counter Ions

scholarly journals Probing G-quadruplex topologies and recognition concurrently in real time and 3D using a dual-app nucleoside probe

2019 ◽  
Vol 47 (12) ◽  
pp. 6059-6072 ◽  
Author(s):  
Ashok Nuthanakanti ◽  
Ishtiyaq Ahmed ◽  
Saddam Y Khatik ◽  
Kayarat Saikrishnan ◽  
Seergazhi G Srivatsan
Keyword(s):  
Nucleic Acid ◽  
Ligand Binding ◽  
Real Time ◽  
Telomeric Dna ◽  
X Ray ◽  
X Ray Crystallography ◽  
New Class ◽  
Loop Region ◽  
Dna Repeat ◽  
G Quadruplex

Abstract Comprehensive understanding of structure and recognition properties of regulatory nucleic acid elements in real time and atomic level is highly important to devise efficient therapeutic strategies. Here, we report the establishment of an innovative biophysical platform using a dual-app nucleoside analog, which serves as a common probe to detect and correlate different GQ structures and ligand binding under equilibrium conditions and in 3D by fluorescence and X-ray crystallography techniques. The probe (SedU) is composed of a microenvironment-sensitive fluorophore and an excellent anomalous X-ray scatterer (Se), which is assembled by attaching a selenophene ring at 5-position of 2′-deoxyuridine. SedU incorporated into the loop region of human telomeric DNA repeat fluorescently distinguished subtle differences in GQ topologies and enabled quantify ligand binding to different topologies. Importantly, anomalous X-ray dispersion signal from Se could be used to determine the structure of GQs. As the probe is minimally perturbing, a direct comparison of fluorescence data and crystal structures provided structural insights on how the probe senses different GQ conformations without affecting the native fold. Taken together, our dual-app probe represents a new class of tool that opens up new experimental strategies to concurrently investigate nucleic acid structure and recognition in real time and 3D.

scholarly journals Same fold, different properties: polarizable molecular dynamics simulations of telomeric and TERRA G-quadruplexes

2019 ◽  
Vol 48 (2) ◽  
pp. 561-575 ◽  
Author(s):  
Justin A Lemkul
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Molecular Dynamics Simulations ◽  
Dipole Moments ◽  
Sequence Motifs ◽  
Telomeric Dna ◽  
Rna Sequences ◽  
Dna And Rna ◽  
Induced Dipole ◽  
Dynamics Simulations

Abstract DNA and RNA sequences rich in guanine can fold into noncanonical structures called G-quadruplexes (GQs), which exhibit a common stem structure of Hoogsteen hydrogen-bonded guanine tetrads and diverse loop structures. GQ sequence motifs are overrepresented in promoters, origins of replication, telomeres, and untranslated regions in mRNA, suggesting roles in modulating gene expression and preserving genomic integrity. Given these roles and unique aspects of different structures, GQs are attractive targets for drug design, but greater insight into GQ folding pathways and the interactions stabilizing them is required. Here, we performed molecular dynamics simulations to study two bimolecular GQs, a telomeric DNA GQ and the analogous telomeric repeat-containing RNA (TERRA) GQ. We applied the Drude polarizable force field, which we show outperforms the additive CHARMM36 force field in both ion retention and maintenance of the GQ folds. The polarizable simulations reveal that the GQs bind bulk K+ ions differently, and that the TERRA GQ accumulates more K+ ions, suggesting different ion interactions stabilize these structures. Nucleobase dipole moments vary as a function of position and also contribute to ion binding. Finally, we show that the TERRA GQ is more sensitive than the telomeric DNA GQ to water-mediated modulation of ion-induced dipole-dipole interactions.

Ligand Binding to Tandem G Quadruplexes from Human Telomeric DNA

ChemBioChem ◽  
2008 ◽  
Vol 9 (16) ◽  
pp. 2583-2587 ◽  
Author(s):  
Li-Ping Bai ◽  
Masaki Hagihara ◽  
Zhi-Hong Jiang ◽  
Kazuhiko Nakatani
Keyword(s):  
Ligand Binding ◽  
Telomeric Dna

scholarly journals Recognition of Chelerythrine to Human Telomeric DNA and RNA G-quadruplexes

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Li-Ping Bai ◽  
Masaki Hagihara ◽  
Kazuhiko Nakatani ◽  
Zhi-Hong Jiang
Keyword(s):  
Telomeric Dna ◽  
Dna And Rna

scholarly journals DNA and RNA Telomeric G-Quadruplexes: What Topology Features Can be Inferred from Ion Mobility Mass Spectrometry?

2019 ◽  
Author(s):  
Valentina D’Atri ◽  
Valerie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Gas Phase ◽  
Ion Mobility Spectrometry ◽  
Ion Mobility ◽  
Native Mass Spectrometry ◽  
Cation Binding ◽  
Telomeric Dna ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Multiple Structures

Maintenance of the telomeres is key to chromosome integrity and cell proliferation. The G-quadruplex structures formed by telomeric DNA and RNA (TTAGGG and UUAGGG repeats, respectively) are key to this process. However, because these sequences are particularly polymorphic, solving high-resolution structures is not always possible, and there is a need for new methodologies to characterize the multiple structures coexisting in solution. In this context, we evaluated whether ion mobility spectrometry coupled to native mass spectrometry could help separate and assign the G-quadruplex topologies. We explored the circular dichroism spectra, multimer formation, cation binding, and ion mobility spectra of several 4-repeat and 8-repeat telomeric DNA and RNA sequences, both in NH<sub>4</sub><sup>+</sup> and in K<sup>+</sup>. In 1 mM K<sup>+</sup> and 100 mM trimethylammonium acetate, all RNAs fold intramolecularly (no multimer). In 8-repeat sequences, the subunits are not independent: in DNA the first subunit disfavors the folding of the second one, whereas in RNA the two subunits fold cooperatively via cation-mediated stacking. Ion mobility spectrometry shows that gas-phase structures keep a memory of the solution ones, but not identical. At the native charge states, the loops can rearrange in a variety of ways (unless they are constrained by pre-formed hydrogen bonds), thereby wrapping the core and masking the strand arrangements. Our study highlights that, to progress towards structural assignment from IM-MS experiments, deeper understanding of the solution-to-gas-phase rearrangement mechanisms is warranted. <br>

scholarly journals Selective and Cooperative Ligand Binding to Antiparallel Human Telomeric DNA G-Quadruplexes

2016 ◽  
Vol 22 (28) ◽  
pp. 9551-9555 ◽  
Author(s):  
Adrien Marchand ◽  
Dominika Strzelecka ◽  
Valerie Gabelica
Keyword(s):  
Ligand Binding ◽  
Telomeric Dna

scholarly journals DNA and RNA Telomeric G-Quadruplexes: What Topology Features Can be Inferred from Ion Mobility Mass Spectrometry?

2019 ◽  
Author(s):  
Valentina D’Atri ◽  
Valerie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Gas Phase ◽  
Ion Mobility Spectrometry ◽  
Ion Mobility ◽  
Native Mass Spectrometry ◽  
Cation Binding ◽  
Telomeric Dna ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Multiple Structures

Maintenance of the telomeres is key to chromosome integrity and cell proliferation. The G-quadruplex structures formed by telomeric DNA and RNA (TTAGGG and UUAGGG repeats, respectively) are key to this process. However, because these sequences are particularly polymorphic, solving high-resolution structures is not always possible, and there is a need for new methodologies to characterize the multiple structures coexisting in solution. In this context, we evaluated whether ion mobility spectrometry coupled to native mass spectrometry could help separate and assign the G-quadruplex topologies. We explored the circular dichroism spectra, multimer formation, cation binding, and ion mobility spectra of several 4-repeat and 8-repeat telomeric DNA and RNA sequences, both in NH<sub>4</sub><sup>+</sup> and in K<sup>+</sup>. In 1 mM K<sup>+</sup> and 100 mM trimethylammonium acetate, all RNAs fold intramolecularly (no multimer). In 8-repeat sequences, the subunits are not independent: in DNA the first subunit disfavors the folding of the second one, whereas in RNA the two subunits fold cooperatively via cation-mediated stacking. Ion mobility spectrometry shows that gas-phase structures keep a memory of the solution ones, but not identical. At the native charge states, the loops can rearrange in a variety of ways (unless they are constrained by pre-formed hydrogen bonds), thereby wrapping the core and masking the strand arrangements. Our study highlights that, to progress towards structural assignment from IM-MS experiments, deeper understanding of the solution-to-gas-phase rearrangement mechanisms is warranted. <br>

scholarly journals Oligonucleotide Models of Telomeric DNA and RNA Form a Hybrid G-quadruplex Structure as a Potential Component of Telomeres

2012 ◽  
Vol 287 (50) ◽  
pp. 41787-41796 ◽  
Author(s):  
Yan Xu ◽  
Takumi Ishizuka ◽  
Jie Yang ◽  
Kenichiro Ito ◽  
Hitoshi Katada ◽  
...  
Keyword(s):  
Telomeric Dna ◽  
Quadruplex Structure ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Potential Component
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