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 Pif1 helicase unfolding of G-quadruplex DNA is highly dependent on sequence and reaction conditions

2018 ◽  
Vol 293 (46) ◽  
pp. 17792-17802 ◽  
Author(s):  
Alicia K. Byrd ◽  
Matthew R. Bell ◽  
Kevin D. Raney
Keyword(s):  
Dna Sequences ◽  
Atp Hydrolysis ◽  
Monovalent Cation ◽  
Product Formation ◽  
Telomeric Dna ◽  
Reaction Conditions ◽  
Specific Sequence ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Pif1 Helicase

In addition to unwinding double-stranded nucleic acids, helicase activity can also unfold noncanonical structures such as G-quadruplexes. We previously characterized Pif1 helicase catalyzed unfolding of parallel G-quadruplex DNA. Here we characterized unfolding of the telomeric G-quadruplex, which can fold into antiparallel and mixed hybrid structures and found significant differences. Telomeric DNA sequences are unfolded more readily than the parallel quadruplex formed by the c-MYC promoter in K+. Furthermore, we found that under conditions in which the telomeric quadruplex is less stable, such as in Na+, Pif1 traps thermally melted quadruplexes in the absence of ATP, leading to the appearance of increased product formation under conditions in which the enzyme is preincubated with the substrate. Stable telomeric G-quadruplex structures were unfolded in a stepwise manner at a rate slower than that of duplex DNA unwinding; however, the slower dissociation from G-quadruplexes compared with duplexes allowed the helicase to traverse more nucleotides than on duplexes. Consistent with this, the rate of ATP hydrolysis on the telomeric quadruplex DNA was reduced relative to that on single-stranded DNA (ssDNA), but less quadruplex DNA was needed to saturate ATPase activity. Under single-cycle conditions, telomeric quadruplex was unfolded by Pif1, but for the c-MYC quadruplex, unfolding required multiple helicase molecules loaded onto the adjacent ssDNA. Our findings illustrate that Pif1-catalyzed unfolding of G-quadruplex DNA is highly dependent on the specific sequence and the conditions of the reaction, including both the monovalent cation and the order of addition.

scholarly journals Increasing the activity of DNAzyme based on the telomeric sequence: 2’-OMe-RNA and LNA modifications

2019 ◽  
Vol 17 (1) ◽  
pp. 1157-1166
Author(s):  
J. Kosman ◽  
K. Żukowski ◽  
B. Juskowiak
Keyword(s):  
Dna Sequences ◽  
Peroxidase Activity ◽  
Telomeric Sequence ◽  
Modified Oligonucleotides ◽  
Biological Applications ◽  
Telomeric Dna ◽  
Nucleotide Analogues ◽  
Dna Oligonucleotides ◽  
G Quadruplex ◽  
Low Activity

Abstract2’-OMe-RNA analogues and LNA point modifications of DNA oligonucleotides were applied for the modulation of the G-quadruplex topology and enhancement of peroxidase activity of the resulting DNAzymes. The effect of the 2’-OMe-RNA analogue was studied for full length modified oligonucleotides with various sequences. In the case of LNA-point modification, we have chosen a telomeric DNA sequence and investigated various numbers of modifications. Our main goal was to prove that the application of these modifications can influence the activity of DNAzyme, especially those, which normally form poor DNAzymes. As an example, we have chosen the telomeric HT22 sequence which is known to form DNAzyme characterized by low activity. In all cases, the DNAzymes formed by a telomeric sequence with the application of the 2’-OMe-RNA analogue as well as LNA-point modification, showed significantly higher peroxidase activity. We were also able to shift the formation of hybrid or antiparallel topology to parallel topology. These results are important for the development of probes for biological applications as well as for the design of probes based on DNA sequences that normally form DNAzymes with low activity. This paper also provides information on how the application of nucleotide analogues can transform the topology of G-quadruplexes.

Interactions of selected gold(iii) complexes with DNA G quadruplexes

2015 ◽  
Vol 44 (8) ◽  
pp. 3633-3639 ◽  
Author(s):  
P. Gratteri ◽  
L. Massai ◽  
E. Michelucci ◽  
R. Rigo ◽  
L. Messori ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Dna Conformation ◽  
Telomeric Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

The interactions of three Au(iii) complexes with human telomeric DNA sequences: Auoxo6 turned out to be very effective in inducing and binding the G-quadruplex DNA conformation.

THE INFLUENCE OF UREA ON G-QUADRUPLEX AND i-MOTIF STRUCTURES IN COMPLEMENTARY DNA SEQUENCES

2020 ◽  
Vol 54 (2 (252)) ◽  
pp. 115-122
Author(s):  
Ye.B. Dalyan ◽  
L.G. Aslanyan ◽  
I.V. Vardanyan
Keyword(s):  
Circular Dichroism ◽  
Dna Sequences ◽  
Thermal Denaturation ◽  
Temperature Scale ◽  
Single Strand ◽  
Structural Transitions ◽  
Telomeric Dna ◽  
Complementary Dna ◽  
G Quadruplex ◽  
Circular Dichroïsm

In the present study, the methods of circular dichroism and UV/Vis spectrophotometry were used to study the influence of urea on the structural transitions i-motif $\leftrightarrows$ unfolded single strand in cytosine-rich ${\text{d[3}^{\prime}\text{-(CCCAAT)}_{3}\text{CCC-5)}^{\prime}]}$ region of telomeric DNA (Tel22C) and G-quadruplex $\leftrightarrows$ unfolded single strand in complementary guanine-rich strand ${\text{d[5}^{\prime}\text{-A(GGGTTA)}_{3}\text{GGG-3}^{\prime}]}$ (Tel22G) at pH 5.5 and 400 mM Na+. Under these conditions, Tel22C and Tel22G were found to form stable i-motif and G-quadruplex structures. It has been shown that urea (0-8 M) destabilizes the i-motif and G-quadruplex structures, but unlike thermal denaturation, it does not destroy the structures completely. The melting processes of G-quadruplex and i-motif are separated in the temperature scale (at any concentration of urea, the melting of the G-quadruplex starts at temperatures where the melting of the i-motifs has already been completed).

scholarly journals Interactions Between Spermine-Derivatized Tentacle Porphyrins and The Human Telomeric DNA G-Quadruplex

2018 ◽  
Vol 19 (11) ◽  
pp. 3686 ◽  
Author(s):  
Navin Sabharwal ◽  
Jessica Chen ◽  
Joo Lee ◽  
Chiara Gangemi ◽  
Alessandro D'Urso ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Binding Constants ◽  
Spectroscopic Studies ◽  
Resonance Light Scattering ◽  
Binding Modes ◽  
Telomeric Dna ◽  
Binding Stoichiometry ◽  
G Quadruplex

G-rich DNA sequences have the potential to fold into non-canonical G-Quadruplex (GQ) structures implicated in aging and human diseases, notably cancers. Because stabilization of GQs at telomeres and oncogene promoters may prevent cancer, there is an interest in developing small molecules that selectively target GQs. Herein, we investigate the interactions of meso-tetrakis-(4-carboxysperminephenyl)porphyrin (TCPPSpm4) and its Zn(II) derivative (ZnTCPPSpm4) with human telomeric DNA (Tel22) via UV-Vis, circular dichroism (CD), and fluorescence spectroscopies, resonance light scattering (RLS), and fluorescence resonance energy transfer (FRET) assays. UV-Vis titrations reveal binding constants of 4.7 × 106 and 1.4 × 107 M−1 and binding stoichiometry of 2–4:1 and 10–12:1 for TCPPSpm4 and ZnTCPPSpm4, respectively. High stoichiometry is supported by the Job plot data, CD titrations, and RLS data. FRET melting indicates that TCPPSpm4 stabilizes Tel22 by 36 ± 2 °C at 7.5 eq., and that ZnTCPPSpm4 stabilizes Tel22 by 33 ± 2 °C at ~20 eq.; at least 8 eq. of ZnTCPPSpm4 are required to achieve significant stabilization of Tel22, in agreement with its high binding stoichiometry. FRET competition studies show that both porphyrins are mildly selective for human telomeric GQ vs duplex DNA. Spectroscopic studies, combined, point to end-stacking and porphyrin self-association as major binding modes. This work advances our understanding of ligand interactions with GQ DNA.

scholarly journals Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences

2014 ◽  
Vol 50 (96) ◽  
pp. 15202-15205 ◽  
Author(s):  
Alex R. O. Cousins ◽  
Dougal Ritson ◽  
Pallavi Sharma ◽  
Malcolm F. G. Stevens ◽  
John E. Moses ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Telomeric Dna ◽  
Ligand Selectivity ◽  
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).

scholarly journals Telomeric DNA sequences in beetle taxa vary with species richness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Prušáková ◽  
Vratislav Peska ◽  
Stano Pekár ◽  
Michal Bubeník ◽  
Lukáš Čížek ◽  
...  
Keyword(s):  
Species Richness ◽  
Dna Sequences ◽  
Genome Instability ◽  
Telomeric Sequence ◽  
Dna Repeats ◽  
Telomeric Dna ◽  
Common Pattern ◽  
Telomeric Sequences ◽  
Genomic Changes ◽  
Protective Structures

AbstractTelomeres are protective structures at the ends of eukaryotic chromosomes, and disruption of their nucleoprotein composition usually results in genome instability and cell death. Telomeric DNA sequences have generally been found to be exceptionally conserved in evolution, and the most common pattern of telomeric sequences across eukaryotes is (TxAyGz)n maintained by telomerase. However, telomerase-added DNA repeats in some insect taxa frequently vary, show unusual features, and can even be absent. It has been speculated about factors that might allow frequent changes in telomere composition in Insecta. Coleoptera (beetles) is the largest of all insect orders and based on previously available data, it seemed that the telomeric sequence of beetles varies to a great extent. We performed an extensive mapping of the (TTAGG)n sequence, the ancestral telomeric sequence in Insects, across the main branches of Coleoptera. Our study indicates that the (TTAGG)n sequence has been repeatedly or completely lost in more than half of the tested beetle superfamilies. Although the exact telomeric motif in most of the (TTAGG)n-negative beetles is unknown, we found that the (TTAGG)n sequence has been replaced by two alternative telomeric motifs, the (TCAGG)n and (TTAGGG)n, in at least three superfamilies of Coleoptera. The diversity of the telomeric motifs was positively related to the species richness of taxa, regardless of the age of the taxa. The presence/absence of the (TTAGG)n sequence highly varied within the Curculionoidea, Chrysomeloidea, and Staphylinoidea, which are the three most diverse superfamilies within Metazoa. Our data supports the hypothesis that telomere dysfunctions can initiate rapid genomic changes that lead to reproductive isolation and speciation.

scholarly journals ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Ching Teng ◽  
Aishwarya Sundaresan ◽  
Ryan O’Hara ◽  
Vincent U. Gant ◽  
Minhua Li ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Genome Stability ◽  
Helicase Domain ◽  
Quadruplex Dna ◽  
Heterochromatin Formation ◽  
Replicative Stress ◽  
G4 Dna ◽  
Mutation Burden ◽  
G Quadruplex ◽  
Dna Replication Stress

AbstractATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease.

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