scholarly journals Exploring the preferential interaction of quercetin with VEGF promoter G-quadruplex DNA and construction of a pH-dependent DNA-based logic gate

RSC Advances ◽  
2017 ◽  
Vol 7 (59) ◽  
pp. 37230-37240 ◽  
Author(s):  
Snehasish Bhattacharjee ◽  
Pradeep K. Sengupta ◽  
Sudipta Bhowmik
Keyword(s):  
Logic Gate ◽  
Quadruplex Dna ◽  
Preferential Interaction ◽  
Double Stranded Dna ◽  
G4 Dna ◽  
G Quadruplex ◽  
Flavonoid Quercetin ◽  
Ph Dependent

The plant flavonoid quercetin (Que) binds more efficiently to VEGF G-quadruplex DNA (G4–DNA) compared to double stranded DNA as well as other G4–DNAs.

pH dependent multifunctional and multiply-configurable logic gate systems based on small molecule G-quadruplex DNA recognition

2013 ◽  
Vol 49 (18) ◽  
pp. 1817 ◽  
Author(s):  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Bibudha Parasar ◽  
Jyotirmayee Dash
Keyword(s):  
Small Molecule ◽  
Logic Gate ◽  
Dna Recognition ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Ph Dependent

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.

scholarly journals Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes

2020 ◽  
Vol 48 (3) ◽  
pp. 1108-1119 ◽  
Author(s):  
Rajendra Kumar ◽  
Karam Chand ◽  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Snehasish Bhattacharjee ◽  
...  
Keyword(s):  
Rational Design ◽  
Dna Structure ◽  
Biological Processes ◽  
Chemical Research ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Future Studies ◽  
G4 Dna ◽  
G Quadruplex ◽  
Fluorescence Light

Abstract G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.

scholarly journals G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma

2018 ◽  
Author(s):  
Yuxiang Wang ◽  
Jie Yang ◽  
Wei Wu ◽  
Rachna Shah ◽  
Carla Danussi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Malignant Glioma ◽  
Model Systems ◽  
Copy Number Alterations ◽  
Molecular Alteration ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
G Quadruplex

AbstractMutational inactivation of ATRX (α-thalassemia mental retardation X-linked) represents a defining molecular alteration in large subsets of malignant glioma. Yet the pathogenic consequences of ATRX deficiency remain unclear, as do tractable mechanisms for its therapeutic targeting. Here we report that ATRX loss in isogenic glioma model systems induces replication stress and DNA damage by way of G-quadruplex (G4) DNA secondary structure. Moreover, these effects are associated with the acquisition of disease-relevant copy number alterations over time. We then demonstrate, both in vitro and in vivo, that ATRX deficiency selectively enhances DNA damage and cell death following chemical G4 stabilization. Finally, we show that G4 stabilization synergizes with other DNA-damaging therapies, including ionizing radiation, in the ATRX-deficient context. Our findings reveal novel pathogenic mechanisms driven by ATRX deficiency in glioma, while also pointing to tangible strategies for drug development.

scholarly journals Macrocyclization of bis-indole quinolines for selective stabilization of G-quadruplex DNA structures

2020 ◽  
Vol 11 (38) ◽  
pp. 10529-10537 ◽  
Author(s):  
Rabindra Nath Das ◽  
Måns Andréasson ◽  
Rajendra Kumar ◽  
Erik Chorell
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
G4 Dna ◽  
Selective Stabilization ◽  
G Quadruplex

Macrocyclization improves the selectivity, affinity, and ability to stabilize G4 DNA structures.

scholarly journals Human Rev1 polymerase disrupts G-quadruplex DNA

2013 ◽  
Vol 42 (5) ◽  
pp. 3272-3285 ◽  
Author(s):  
Sarah Eddy ◽  
Amit Ketkar ◽  
Maroof K. Zafar ◽  
Leena Maddukuri ◽  
Jeong-Yun Choi ◽  
...  
Keyword(s):  
Genome Maintenance ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G4 Dna ◽  
G Quadruplex ◽  
Steady State Rate ◽  
Dna Substrates ◽  
Successful Replication ◽  
Y Family

Abstract The Y-family DNA polymerase Rev1 is required for successful replication of G-quadruplex DNA (G4 DNA) in higher eukaryotes. Here we show that human Rev1 (hRev1) disrupts G4 DNA structures and prevents refolding in vitro. Nucleotidyl transfer by hRev1 is not necessary for mechanical unfolding to occur. hRev1 binds G4 DNA substrates with Kd,DNA values that are 4–15-fold lower than those of non-G4 DNA substrates. The pre-steady-state rate constant of deoxycytidine monophosphate (dCMP) insertion opposite the first tetrad-guanine by hRev1 is ∼56% as fast as that observed for non-G4 DNA substrates. Thus, hRev1 can promote fork progression by either dislodging tetrad guanines to unfold the G4 DNA, which could assist in extension by other DNA polymerases, or hRev1 can prevent refolding of G4 DNA structures. The hRev1 mechanism of action against G-quadruplexes helps explain why replication progress is impeded at G4 DNA sites in Rev1-deficient cells and illustrates another unique feature of this enzyme with important implications for genome maintenance.

scholarly journals G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs

2017 ◽  
Vol 4 (1) ◽  
pp. 10-32 ◽  
Author(s):  
Qian Cao ◽  
Yi Li ◽  
Eva Freisinger ◽  
Peter Z. Qin ◽  
Roland K. O. Sigel ◽  
...  
Keyword(s):  
Metal Complexes ◽  
Anticancer Drugs ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
G Quadruplex

This review summarizes the recent development of G4 DNA targeted metal complexes and discusses their potential as anticancer drugs.

Spectroscopic Studies on the Binding Properties of Ofloxacin and Human Telomeric G-Quadruplex DNA

2013 ◽  
Vol 634-638 ◽  
pp. 1062-1065 ◽  
Author(s):  
Xu Jian Luo ◽  
Qi Pin Qin ◽  
Yu Lan Li ◽  
Yan Yang
Keyword(s):  
Spectral Analysis ◽  
Fluorescence Emission ◽  
Spectroscopic Studies ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
G Quadruplex ◽  
Shoulder Peak ◽  
Binding Intensity ◽  
Dna Complex

The binding of ofloxacin with human telomeric G-quadruplex DNA, Htel-G4-DNA and Htel-3-G4-DNA were examined by Fluorescence and CD spectroscopic methods. In the Fluorescence emission spectral analysis, the addition of ofloxacin induced significant quenching on the fluorescence emission of TO-G4-DNA complex. The fluorescence spectral analysis indicated that ofloxacin exhibited higher binding affinity and binding intensity to Htel-G4-DNA than Htel-3-G4-DNA. In the CD spectral analysis, the interaction with ofloxacin did not disturb the characteristic absorption of Htel-G4-DNA at 290 nm corresponding to its antiparallel form, and only slightly increased the positive absorption at 270 nm as shoulder peak, which suggests the antiparallel structure of G-quadruplex can remain stable in the presence of ofloxacin

scholarly journals Targeting G-quadruplex DNA with synthetic dendritic peptide: modulation of the proliferation of human cancer cells

RSC Advances ◽  
2020 ◽  
Vol 10 (44) ◽  
pp. 26388-26396
Author(s):  
Soumi Biswas ◽  
Satyabrata Samui ◽  
Apurba K. Das ◽  
Sanjeev Pasadi ◽  
K. Muniyappa ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Quadruplex Dna ◽  
Human Cancer Cells ◽  
G4 Dna ◽  
G Quadruplex ◽  
Peptide Targeting

A synthetic dendritic peptide, targeting human telomeric G4 DNA, inhibits the telomerase and lessens the proliferation of human cancer cells.

Sign in / Sign up

Export Citation Format

Share Document