Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing

2018 ◽  
Vol 13 (3) ◽  
pp. 551-564 ◽  
Author(s):  
Robert Hänsel-Hertsch ◽  
Jochen Spiegel ◽  
Giovanni Marsico ◽  
David Tannahill ◽  
Shankar Balasubramanian
Keyword(s):  
High Throughput ◽  
Chromatin Immunoprecipitation ◽  
High Throughput Sequencing ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Genome Wide ◽  
G Quadruplex

scholarly journals DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions

2021 ◽  
Author(s):  
Anirban Ghosh ◽  
Eric Largy ◽  
Valérie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Drug Targets ◽  
Native Mass Spectrometry ◽  
Drug Binding ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Nmr Structures ◽  
G Quadruplex ◽  
Screening Assays

Abstract G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (Tm), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).

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 Specific Photocleavage Activity of N ‐Methylmesoporphyrin IX on G‐Quadruplex DNA Structures

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Ruby A Escobedo ◽  
Kimberly J Long ◽  
Dominic N McBrayer ◽  
Michelle Schoonover ◽  
Sean M Kerwin
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex

scholarly journals PRIME-3D2D is a 3D2D model to predict binding sites of protein–RNA interaction

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Juan Xie ◽  
Jinfang Zheng ◽  
Xu Hong ◽  
Xiaoxue Tong ◽  
Shiyong Liu
Keyword(s):  
Full Advantage ◽  
High Throughput ◽  
Binding Sites ◽  
High Throughput Sequencing ◽  
Secondary Structures ◽  
Biological Processes ◽  
Genome Wide ◽  
Rna Interaction ◽  
Rna Complexes ◽  
Better Than

AbstractProtein-RNA interaction participates in many biological processes. So, studying protein–RNA interaction can help us to understand the function of protein and RNA. Although the protein–RNA 3D3D model, like PRIME, was useful in building 3D structural complexes, it can’t be used genome-wide, due to lacking RNA 3D structures. To take full advantage of RNA secondary structures revealed from high-throughput sequencing, we present PRIME-3D2D to predict binding sites of protein–RNA interaction. PRIME-3D2D is almost as good as PRIME at modeling protein–RNA complexes. PRIME-3D2D can be used to predict binding sites on PDB data (MCC = 0.75/0.70 for binding sites in protein/RNA) and transcription-wide (MCC = 0.285 for binding sites in RNA). Testing on PDB and yeast transcription-wide data show that PRIME-3D2D performs better than other binding sites predictor. So, PRIME-3D2D can be used to predict the binding sites both on PDB and genome-wide, and it’s freely available.

scholarly journals N-methyl mesoporphyrin IX as a highly selective light-up probe for G-quadruplex DNA

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1195-1215 ◽  
Author(s):  
Ariana Yett ◽  
Linda Yingqi Lin ◽  
Dana Beseiso ◽  
Joanne Miao ◽  
Liliya A. Yatsunyk
Keyword(s):  
Optical Properties ◽  
Small Molecules ◽  
Genomic Stability ◽  
Water Soluble ◽  
Biological Processes ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
High Fluorescence

[Formula: see text]-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules ([Formula: see text] ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

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