Identification of novel interactors of human telomeric G-quadruplex DNA

2015 ◽  
Vol 51 (14) ◽  
pp. 2964-2967 ◽  
Author(s):  
Bruno Pagano ◽  
Luigi Margarucci ◽  
Pasquale Zizza ◽  
Jussara Amato ◽  
Nunzia Iaccarino ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Dna Structure ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
In Cells

Starting from a chemoproteomic-driven approach, novel human telomeric G-quadruplex binding proteins were identified that directly bind the DNA structure in vitro and colocalize with such structures in cells.

scholarly journals A red-NIR fluorescent dye detecting nuclear DNA G-quadruplexes: in vitro analysis and cell imaging

2017 ◽  
Vol 53 (14) ◽  
pp. 2268-2271 ◽  
Author(s):  
F. Doria ◽  
M. Nadai ◽  
M. Zuffo ◽  
R. Perrone ◽  
M. Freccero ◽  
...  
Keyword(s):  
Cell Imaging ◽  
Nuclear Dna ◽  
Fluorescent Dye ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
In Cells

Light-up of nuclear G-quadruplex DNA in cells by an aggregating and red/NIR emitting dye.

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 Human telomere double G-quadruplex recognition by berberine-bisquinolinium imaging conjugates in vitro and in cells

2020 ◽  
Vol 158 ◽  
pp. 1299-1309
Author(s):  
Ting-Cong Liao ◽  
Tian-Zhu Ma ◽  
Suo-Bin Chen ◽  
Agostino Cilibrizzi ◽  
Meng-Jia Zhang ◽  
...  
Keyword(s):  
G Quadruplex ◽  
Human Telomere ◽  
In Cells

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 VEZF1–guanine quadruplex DNA interaction regulates alternative polyadenylation and detyrosinase activity of VASH1

2020 ◽  
Vol 48 (21) ◽  
pp. 11994-12003
Author(s):  
Lin Li ◽  
Preston Williams ◽  
Zi Gao ◽  
Yinsheng Wang
Keyword(s):  
Binding Protein ◽  
Umbilical Vein ◽  
Alternative Polyadenylation ◽  
Dna Interaction ◽  
Vascular Endothelial ◽  
Quadruplex Dna ◽  
Guanine Quadruplex ◽  
Umbilical Vein Endothelial Cells ◽  
In Cells

Abstract Vascular endothelial zinc finger 1 (VEZF1) plays important roles in endothelial lineage definition and angiogenesis. Vasohibins 1 and 2 (VASH1 and VASH2) can form heterodimers with small vasohibin-binding protein (SVBP) and were recently shown to regulate angiogenesis by acting as tubulin detyrosinases. Here, we showed that VEZF1 binds directly with DNA guanine quadruplex (G quadruplex, G4) structures in vitro and in cells, which modulates the levels of the two isoforms of VASH1 mRNA. Disruption of this interaction, through genetic depletion of VEZF1 or treatment of cells with G4-stabilizing small molecules, led to increased production of the long over short isoform of VASH1 (i.e. VASH1A and VASH1B, respectively) mRNA and elevated tubulin detyrosinase activity in cells. Moreover, disruption of VEZF1-G4 interactions in human umbilical vein endothelial cells resulted in diminished angiogenesis. These results suggest that the interaction between VEZF1 and G4 structures assumes a crucial role in angiogenesis, which occurs through regulating the relative levels of the two isoforms of VASH1 mRNA and the detyrosinase activity of the VASH1-SVBP complex. Together, our work revealed VEZF1 as a G4-binding protein, identified a novel regulatory mechanism for tubulin detyrosinase, and illustrated that the VEZF1- and VASH1-mediated angiogenesis pathways are functionally connected.

scholarly journals A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia differentiation

2015 ◽  
Vol 6 (1) ◽  
pp. e1610-e1610 ◽  
Author(s):  
X Gao ◽  
W Ma ◽  
J Nie ◽  
C Zhang ◽  
J Zhang ◽  
...  
Keyword(s):  
Dna Structure ◽  
Quadruplex Dna ◽  
G Quadruplex

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.

Sign in / Sign up

Export Citation Format

Share Document