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.

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 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 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.

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 G-rich telomeric and ribosomal DNA sequences from the fission yeast genome form stable G-quadruplex DNA structuresin vitroand are unwound by the Pfh1 DNA helicase

2016 ◽  
Vol 44 (13) ◽  
pp. 6213-6231 ◽  
Author(s):  
Marcus Wallgren ◽  
Jani B. Mohammad ◽  
Kok-Phen Yan ◽  
Parham Pourbozorgi-Langroudi ◽  
Mahsa Ebrahimi ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Ribosomal Dna ◽  
Dna Sequences ◽  
Dna Helicase ◽  
Yeast Genome ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals Evidences for Piperine inhibiting cancer by targeting human G-quadruplex DNA sequences

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Arpita Tawani ◽  
Ayeman Amanullah ◽  
Amit Mishra ◽  
Amit Kumar
Keyword(s):  
Dna Sequences ◽  
Quadruplex Dna ◽  
G Quadruplex

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.

scholarly journals 9,10-Bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene: Synthesis and G-quadruplex Selectivity

Molbank ◽  
10.3390/m1138 ◽  
2020 ◽  
Vol 2020 (2) ◽  
pp. M1138
Author(s):  
Giovanni Ribaudo ◽  
Alberto Ongaro ◽  
Erika Oselladore ◽  
Giuseppe Zagotto ◽  
Maurizio Memo ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Binding Mode ◽  
Sonogashira Reaction ◽  
Ionization Mass ◽  
Quadruplex Dna ◽  
Anthracene Derivative ◽  
Double Stranded Dna ◽  
G Quadruplex ◽  
A3 Coupling ◽  
Hydroxyethyl Piperazine

G-quadruplex DNA is the target of several natural and synthetic small molecules with antiproliferative and antiviral activity. We here report the synthesis through Sonogashira reaction and A3 coupling of a disubstituted anthracene derivative, 9,10-bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene. The binding of this compound to G-quadruplex and double stranded DNA sequences was evaluated using electrospray ionization mass spectrometry (ESI-MS), demonstrating selectivity for the first structure. The interaction pattern of the ligand with G-quadruplex was investigated by molecular docking and stacking was found to be the preferred binding mode.

scholarly journals Enantiomeric copper based anticancer agents promoting sequence-selective cleavage of G-quadruplex telomeric DNA and non-random cleavage of plasmid DNA

Metallomics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 988-999 ◽  
Author(s):  
Sabiha Parveen ◽  
J. A. Cowan ◽  
Zhen Yu ◽  
Farukh Arjmand
Keyword(s):  
Anticancer Agents ◽  
Plasmid Dna ◽  
Telomeric Dna ◽  
Quadruplex Dna ◽  
Dna Cleaving ◽  
G Quadruplex

Copper-based enantiomeric anticancer agents (1S and 1R) were synthesized and studied as sequence-selective G-quadruplex DNA cleaving agents.

Human Pif1 helicase is a G-quadruplex DNA-binding protein with G-quadruplex DNA-unwinding activity

2010 ◽  
Vol 430 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Cyril M. Sanders
Keyword(s):  
Dna Binding ◽  
Dna Sequences ◽  
Genome Stability ◽  
Dna Helicase ◽  
Dna Unwinding ◽  
Helicase Domain ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
G Quadruplex ◽  
Pif1 Helicase

Pif1 proteins are helicases that in yeast are implicated in the maintenance of genome stability. One activity of Saccharomyces cerevisiae Pif1 is to stabilize DNA sequences that could otherwise form deleterious G4 (G-quadruplex) structures by acting as a G4 resolvase. The present study shows that human Pif1 (hPif1, nuclear form) is a G4 DNA-binding and resolvase protein and that these activities are properties of the conserved helicase domain (amino acids 206–620 of 641, hPifHD). hPif1 preferentially bound synthetic G4 DNA relative to ssDNA (single-stranded DNA), dsDNA (double-stranded DNA) and a partially single-stranded duplex DNA helicase substrate. G4 DNA unwinding, but not binding, required an extended (>10 nucleotide) 5′ ssDNA tail, and in competition assays, G4 DNA was an ineffective suppressor of helicase activity compared with ssDNA. These results suggest a distinction between the determinants of G4 DNA binding and the ssDNA interactions required for helicase action and that hPif1 may act on G4 substrates by binding alone or as a resolvase. Human Pif1 could therefore have a role in processing G4 structures that arise in the single-stranded nucleic acid intermediates formed during DNA replication and gene expression.

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