scholarly journals Insights into telomeric G-quadruplex DNA recognition by HMGB1 protein

2019 ◽  
Vol 47 (18) ◽  
pp. 9950-9966 ◽  
Author(s):  
Jussara Amato ◽  
Linda Cerofolini ◽  
Diego Brancaccio ◽  
Stefano Giuntini ◽  
Nunzia Iaccarino ◽  
...  
Keyword(s):  
Biological Effects ◽  
Dna Recognition ◽  
Subcellular Location ◽  
Biological Data ◽  
Telomere Maintenance ◽  
Hmgb1 Protein ◽  
Bent Dna ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Negative Tumor

Abstract HMGB1 is a ubiquitous non-histone protein, which biological effects depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription and telomere maintenance. HMGB1 has been reported to bind preferentially to bent DNA as well as to noncanonical DNA structures like 4-way junctions and, more recently, to G-quadruplexes. These are four-stranded conformations of nucleic acids involved in important cellular processes, including telomere maintenance. In this frame, G-quadruplex recognition by specific proteins represents a key event to modulate physiological or pathological pathways. Herein, to get insights into the telomeric G-quadruplex DNA recognition by HMGB1, we performed detailed biophysical studies complemented with biological analyses. The obtained results provided information about the molecular determinants for the interaction and showed that the structural variability of human telomeric G-quadruplex DNA may have significant implications in HMGB1 recognition. The biological data identified HMGB1 as a telomere-associated protein in both telomerase-positive and -negative tumor cells and showed that HMGB1 gene silencing in such cells induces telomere DNA damage foci. Altogether, these findings provide a deeper understanding of telomeric G-quadruplex recognition by HMGB1 and suggest that this protein could actually represent a new target for cancer therapy.

scholarly journals Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

Molecules ◽  
2013 ◽  
Vol 18 (11) ◽  
pp. 13588-13607 ◽  
Author(s):  
Rupesh Nanjunda ◽  
Eric Owens ◽  
Leah Mickelson ◽  
Tyler Dost ◽  
Ekaterina Stroeva ◽  
...  
Keyword(s):  
Dna Recognition ◽  
Quadruplex Dna ◽  
New Class ◽  
G Quadruplex

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 Ruthenium–arene complexes bearing naphthyl-substituted 1,3-dioxoindan-2-carboxamides ligands for G-quadruplex DNA recognition

2019 ◽  
Vol 48 (32) ◽  
pp. 12040-12049 ◽  
Author(s):  
Laura A. Hager ◽  
Stephan Mokesch ◽  
Claudia Kieler ◽  
Silvia Alonso-de Castro ◽  
Dina Baier ◽  
...  
Keyword(s):  
Dna Recognition ◽  
Arene Complexes ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
Ruthenium Arene

Ru(ii) arene complexes with 1,3-dioxoindan-2-carboxamides ligands bearing pendant naphthyl-groups designed to bind G-quadruplex DNA structures by both stacking and coordinating interactions.

scholarly journals “One Ring to Bind Them All”—Part I: The Efficiency of the Macrocyclic Scaffold for G-Quadruplex DNA Recognition

2010 ◽  
Vol 2010 ◽  
pp. 1-19 ◽  
Author(s):  
David Monchaud ◽  
Anton Granzhan ◽  
Nicolas Saettel ◽  
Aurore Guédin ◽  
Jean-Louis Mergny ◽  
...  
Keyword(s):  
State Of The Art ◽  
Biological Activities ◽  
Dna Recognition ◽  
Dna Conformation ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Current State ◽  
G Quadruplex ◽  
Biological Aspects

Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the “standard” B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes), and in addressing both synthetic issues and biological aspects.

scholarly journals G-Quadruplex DNA Motifs in the Malaria ParasitePlasmodium falciparumand Their Potential as Novel Antimalarial Drug Targets

2018 ◽  
Vol 62 (3) ◽  
Author(s):  
Lynne M. Harris ◽  
Katelyn R. Monsell ◽  
Florian Noulin ◽  
M. Toyin Famodimu ◽  
Nicolas Smargiasso ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Drug Targets ◽  
Human Cells ◽  
Telomere Maintenance ◽  
Content Type ◽  
Quadruplex Dna ◽  
Rna Translation ◽  
G Quadruplex ◽  
First Time

ABSTRACTG-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occurin vivoin the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or, in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasitePlasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes. We show that despite this paucity of putative G-quadruplex-forming sequences,P. falciparumparasites are sensitive to several G-quadruplex-stabilizing drugs, including quarfloxin, which previously reached phase 2 clinical trials as an anticancer drug. Quarfloxin has a rapid initial rate of kill and is active against ring stages as well as replicative stages of intraerythrocytic development. We show that several G-quadruplex-stabilizing drugs, including quarfloxin, can suppress the transcription of a G-quadruplex-containing reporter gene inP. falciparumbut that quarfloxin does not appear to disrupt the transcription of rRNAs, which was proposed as its mode of action in both human cells and trypanosomes. These data suggest that quarfloxin has potential for repositioning as an antimalarial with a novel mode of action. Furthermore, G-quadruplex biology inP. falciparummay present a target for development of other new antimalarial drugs.

scholarly journals Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1

2020 ◽  
Vol 48 (8) ◽  
pp. 4562-4571 ◽  
Author(s):  
Anna Traczyk ◽  
Chong Wai Liew ◽  
David James Gill ◽  
Daniela Rhodes
Keyword(s):  
Dna Binding ◽  
Dna Recognition ◽  
Binding Domain ◽  
Telomere Maintenance ◽  
Structural Basis ◽  
Dna Binding Domain ◽  
Double Stranded Dna ◽  
G Quadruplex ◽  
Quadruplex Formation ◽  
Telomeric Protein

Abstract G-quadruplexes are four-stranded nucleic acid structures involved in multiple cellular pathways including DNA replication and telomere maintenance. Such structures are formed by G-rich DNA sequences typified by telomeric DNA repeats. Whilst there is evidence for proteins that bind and regulate G-quadruplex formation, the molecular basis for this remains poorly understood. The budding yeast telomeric protein Rap1, originally identified as a transcriptional regulator functioning by recognizing double-stranded DNA binding sites, was one of the first proteins to be discovered to also bind and promote G-quadruplex formation in vitro. Here, we present the 2.4 Å resolution crystal structure of the Rap1 DNA-binding domain in complex with a G-quadruplex. Our structure not only provides a detailed insight into the structural basis for G-quadruplex recognition by a protein, but also gives a mechanistic understanding of how the same DNA-binding domain adapts to specifically recognize different DNA structures. The key observation is the DNA-recognition helix functions in a bimodal manner: In double-stranded DNA recognition one helix face makes electrostatic interactions with the major groove of DNA, whereas in G-quadruplex recognition a different helix face is used to make primarily hydrophobic interactions with the planar face of a G-tetrad.

scholarly journals A biochemical and biophysical model of G-quadruplex DNA recognition by positive coactivator of transcription 4

2017 ◽  
Vol 292 (23) ◽  
pp. 9567-9582 ◽  
Author(s):  
Wezley C. Griffin ◽  
Jun Gao ◽  
Alicia K. Byrd ◽  
Shubeena Chib ◽  
Kevin D. Raney
Keyword(s):  
Dna Recognition ◽  
Biophysical Model ◽  
Quadruplex Dna ◽  
G Quadruplex

G-quadruplex DNA recognition by nucleophosmin: New insights from protein dissection

2014 ◽  
Vol 1840 (6) ◽  
pp. 2050-2059 ◽  
Author(s):  
Pasqualina Liana Scognamiglio ◽  
Concetta Di Natale ◽  
Marilisa Leone ◽  
Mattia Poletto ◽  
Luigi Vitagliano ◽  
...  
Keyword(s):  
Dna Recognition ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA

2021 ◽  
Author(s):  
James Edwards-Smallbone ◽  
Anders L Jensen ◽  
Lydia E Roberts ◽  
Francis Isidore Garcia Totanes ◽  
Sarah R Hart ◽  
...  
Keyword(s):  
Rna Binding ◽  
Protozoan Parasite ◽  
Telomere Maintenance ◽  
Model Systems ◽  
Quadruplex Dna ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Associated Proteins

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via Proteomics of Isolated Chromatin fragments, applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.

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