Energetic Basis of Human Telomeric DNA Folding into G-Quadruplex Structures

2012 ◽  
Vol 134 (23) ◽  
pp. 9657-9663 ◽  
Author(s):  
Matjaž Bončina ◽  
Jurij Lah ◽  
Iztok Prislan ◽  
Gorazd Vesnaver
Keyword(s):  
Telomeric Dna ◽  
Dna Folding ◽  
G Quadruplex

scholarly journals PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex

2021 ◽  
Vol 22 (2) ◽  
pp. 749
Author(s):  
Patricia B. Gratal ◽  
Julia G. Quero ◽  
Adrián Pérez-Redondo ◽  
Zoila Gándara ◽  
Lourdes Gude
Keyword(s):  
Equilibrium Dialysis ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
The Novel ◽  
X Ray Diffraction ◽  
Telomeric Dna ◽  
Healthy Human ◽  
Quadruplex Dna ◽  
Step Procedure ◽  
G Quadruplex

A novel quadruplex ligand based on 1,10-phenanthroline and incorporating two guanyl hydrazone functionalities, PhenQE8, is reported herein. Synthetic access was gained in a two-step procedure with an overall yield of 61%. X-ray diffraction studies revealed that PhenQE8 can adopt an extended conformation that may be optimal to favor recognition of quadruplex DNA. DNA interactions with polymorphic G-quadruplex telomeric structures were studied by different techniques, such as Fluorescence resonance energy transfer (FRET) DNA melting assays, circular dichroism and equilibrium dialysis. Our results reveal that the novel ligand PhenQE8 can efficiently recognize the hybrid quadruplex structures of the human telomeric DNA, with high binding affinity and quadruplex/duplex selectivity. Moreover, the compound shows significant cytotoxic activity against a selected panel of cultured tumor cells (PC-3, HeLa and MCF-7), whereas its cytotoxicity is considerably lower in healthy human cells (HFF-1 and RPWE-1).

Research Progress in the Typical Structure of Human Telomeric G-Quadruplex

2014 ◽  
Vol 955-959 ◽  
pp. 419-422
Author(s):  
Gui Lin Liu ◽  
Yan Ping Ding ◽  
Yan Ling Wu ◽  
Wen Zhang
Keyword(s):  
Cell Cycle ◽  
Dna Sequences ◽  
Research Progress ◽  
Human Chromosomes ◽  
Telomeric Dna ◽  
Typical Structure ◽  
Special Sequence ◽  
Physiological Processes ◽  
G Quadruplex ◽  
Small Molecule Ligands

Telomeric DNA of human chromosomes plays a significant role in physiological processes such as cell cycle, aging, cancer and genetic stability due to its special sequence and structure. The research on small molecule ligands targeting G-quadruplex formed by such special sequence has attracted considerable attention, and has achieved great breakthrough. In this paper, we summarize the DNA sequences and structures of three kinds of typical human telomeric G-quadruplex, providing an important reference for further research.

scholarly journals Telomeric G-Quadruplexes: From Human to Tetrahymena Repeats

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Erika Demkovičová ◽  
Ľuboš Bauer ◽  
Petra Krafčíková ◽  
Katarína Tlučková ◽  
Petra Tóthova ◽  
...  
Keyword(s):  
Life Cycle ◽  
Base Substitution ◽  
Telomeric Dna ◽  
Purine Base ◽  
Telomeric Sequences ◽  
G Quadruplex ◽  
The Stability ◽  
Scientific Value ◽  
The Relationship ◽  
Adenine Base

The human telomeric and protozoal telomeric sequences differ only in one purine base in their repeats; TTAGGG in telomeric sequences; and TTGGGG in protozoal sequences. In this study, the relationship between G-quadruplexes formed from these repeats and their derivatives is analyzed and compared. The human telomeric DNA sequence G3(T2AG3)3 and related sequences in which each adenine base has been systematically replaced by a guanine were investigated; the result is Tetrahymena repeats. The substitution does not affect the formation of G-quadruplexes but may cause differences in topology. The results also show that the stability of the substituted derivatives increased in sequences with greater number of substitutions. In addition, most of the sequences containing imperfections in repeats which were analyzed in this study also occur in human and Tetrahymena genomes. Generally, the presence of G-quadruplex structures in any organism is a source of limitations during the life cycle. Therefore, a fuller understanding of the influence of base substitution on the structural variability of G-quadruplexes would be of considerable scientific value.

scholarly journals The Interaction of Telomeric DNA and C-myc22 G-Quadruplex with 11 Natural Alkaloids

2012 ◽  
Vol 22 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Xiaohui Ji ◽  
Hongxia Sun ◽  
Huaxi Zhou ◽  
Junfeng Xiang ◽  
Yalin Tang ◽  
...  
Keyword(s):  
Telomeric Dna ◽  
G Quadruplex

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 G-quadruplex Stabilization Fuels the ALT Pathway in ALT-positive Osteosarcoma Cells

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 304 ◽  
Author(s):  
Roberta Amato ◽  
Martina Valenzuela ◽  
Francesco Berardinelli ◽  
Erica Salvati ◽  
Carmen Maresca ◽  
...  
Keyword(s):  
Dna Damage ◽  
Sister Chromatid Exchanges ◽  
Telomere Maintenance ◽  
Osteosarcoma Cell ◽  
Telomeric Dna ◽  
Replicative Stress ◽  
Alternative Lengthening ◽  
G Quadruplex ◽  
Reduce Cell Proliferation ◽  
The Impact

Most human tumors maintain telomere lengths by telomerase, whereas a portion of them (10–15%) uses a mechanism named alternative lengthening of telomeres (ALT). The telomeric G-quadruplex (G4) ligand RHPS4 is known for its potent antiproliferative effect, as shown in telomerase-positive cancer models. Moreover, RHPS4 is also able to reduce cell proliferation in ALT cells, although the influence of G4 stabilization on the ALT mechanism has so far been poorly investigated. Here we show that sensitivity to RHPS4 is comparable in ALT-positive (U2OS; SAOS-2) and telomerase-positive (HOS) osteosarcoma cell lines, unlinking the telomere maintenance mechanism and RHPS4 responsiveness. To investigate the impact of G4 stabilization on ALT, the cardinal ALT hallmarks were analyzed. A significant induction of telomeric doublets, telomeric clusterized DNA damage, ALT-associated Promyelocytic Leukaemia-bodies (APBs), telomere sister chromatid exchanges (T-SCE) and c-circles was found exclusively in RHPS4-treated ALT cells. We surmise that RHPS4 affects ALT mechanisms through the induction of replicative stress that in turn is converted in DNA damage at telomeres, fueling recombination. In conclusion, our work indicates that RHPS4-induced telomeric DNA damage promotes overactivation of telomeric recombination in ALT cells, opening new questions on the therapeutic employment of G4 ligands in the treatment of ALT positive tumors.

scholarly journals Folding Kinetics of Multiple G-Quadruplex Telomeric DNA Structures

2020 ◽  
Vol 118 (3) ◽  
pp. 335a
Author(s):  
Emil L. Kristoffersen ◽  
Andrea Coletta ◽  
Line Lund ◽  
Birgit Schiøtt ◽  
Victoria Birkedal
Keyword(s):  
Folding Kinetics ◽  
Telomeric Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
Kinetics Of

Electrochemical selection of G-quadruplex-binding ligands based on structure-switching of telomeric DNA

2011 ◽  
Vol 3 (6) ◽  
pp. 1270 ◽  
Author(s):  
Xiao-Qin Liu ◽  
Yan Jin ◽  
Yuexia Wang ◽  
Yunxia Qiao
Keyword(s):  
Telomeric Dna ◽  
G Quadruplex ◽  
Structure Switching ◽  
Selection Of

scholarly journals Evaluation of the Interaction between Long Telomeric DNA and Macrocyclic Hexaoxazole (6OTD) Dimer of a G-quadruplex Ligand

Molecules ◽  
2013 ◽  
Vol 18 (4) ◽  
pp. 4328-4341 ◽  
Author(s):  
Keisuke Iida ◽  
Satoki Majima ◽  
Takahiro Nakamura ◽  
Hiroyuki Seimiya ◽  
Kazuo Nagasawa
Keyword(s):  
Telomeric Dna ◽  
G Quadruplex
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