scholarly journals Més enllà de la doble hèlix: L’estructura G-quàdruplex de l’ADN

Author(s):  
Isabel Pont ◽  
Jorge Gonzàlez-Garcia

DNA is the fundamental biomolecule needed for correct cell functioning and, until very recently, it was associated to the double helix structure discovered over 70 years ago by Crick, Watson, and Franklin. However, other DNA structures and conformations have been described, like G-quadruplexes. These G-quadruplexes are formed in regions of the genome that are rich in guanine. They have tetramer structure and control biological processes such as genetic expression, protection against ageing, or the transmission of neural information. In this document, we describe their chemical and structural characteristics, besides presenting their main cellular functions. Lastly, we present G-quadruplexes as molecular targets for future cancer therapies.

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yubin Li ◽  
Jiaming Yuan ◽  
Zexi Xu

A C-Ag+-C structure-based fluorescence biosensor with novel combination design of exonuclease III (Exo III) dual-recycling amplification is proposed for the application of silver ions (Ag+) detection. Since oligo-1 involves C-C mismatches, the presence of Ag+ can be captured to form C-Ag+-C base pairs, which results in a double-helix structure with a blunt terminus. The double-helix structure can be cleaved by EXO III to release short mononucleotide fragments (trigger DNA) and Ag+. Released Ag+ can form new bindings with oligo-1, and other trigger DNA can be produced in the digestion cycles. Hybridization with the signal DNA (oligo-2) transforms a trigger DNA into double-stranded DNA with blunt terminus which can be cleaved by Exo III to reproduce the trigger DNA and form guanine- (G-) quadruplex DNA. The trigger DNA returns free to the solution and hybridizes with another signal DNA, which realizes the dual-recycling amplification. The G-quadruplex DNA can be reported by N-methylmesoporphyrin IX (NMM), a specific G-quadruplex DNA fluorochrome. This method allows Ag+ to be determined in the 5 to 1500 pmol/L concentration range, with a 2 pmol/L detection limit, and it has been successfully applied to the detection of Ag+ in real samples.


2019 ◽  
Vol 47 (15) ◽  
pp. 8272-8281 ◽  
Author(s):  
Fernaldo Richtia Winnerdy ◽  
Blaž Bakalar ◽  
Arijit Maity ◽  
J Jeya Vandana ◽  
Yves Mechulam ◽  
...  

AbstractAnalogous to the B- and Z-DNA structures in double-helix DNA, there exist both right- and left-handed quadruple-helix (G-quadruplex) DNA. Numerous conformations of right-handed and a few left-handed G-quadruplexes were previously observed, yet they were always identified separately. Here, we present the NMR solution and X-ray crystal structures of a right- and left-handed hybrid G-quadruplex. The structure reveals a stacking interaction between two G-quadruplex blocks with different helical orientations and displays features of both right- and left-handed G-quadruplexes. An analysis of loop mutations suggests that single-nucleotide loops are preferred or even required for the left-handed G-quadruplex formation. The discovery of a right- and left-handed hybrid G-quadruplex further expands the polymorphism of G-quadruplexes and is potentially useful in designing a left-to-right junction in G-quadruplex engineering.


2021 ◽  
Author(s):  
Georgios C Stefos ◽  
Georgios Theodorou ◽  
Ioannis Politis

G-Quadruplex structures are non-B DNA structures that occur in regions carrying short runs of guanines. They are implicated in several biological processes including transcription, translation, replication and telomere maintenance as well as in several pathological conditions like cancer and thus they have gained the attention of the scientific community. The rise of the -omics era significantly affected the G-quadruplex research and the genome-wide characterization of G-Quadruplexes has been rendered a necessary first step towards applying genomics approaches for their study. While in human and several model organisms there is a considerable number of works studying genome-wide the DNA motifs with potential to form G-quadruplexes (G4-motifs), there is a total absence of any similar studies regarding livestock animals. The objectives of the present study were to provide a detailed characterization of the bovine genic G4-motifs distribution and properties and to suggest a possible mechanism for the delivery of G4 motifs in the genes. Our data indicate that the distribution of G4s within bovine genes and the annotation of said genes to Gene Ontology terms are similar to what is already shown for other organisms. By investigating their structural characteristics and polymorphism, it is obvious that the overall stability of the putative quadruplex structures is in line with the current notion in the G4 field. Similarly to human, the bovine G4s are overrepresented in specific LINE repeat elements, the L1_BTs in the case of cattle. We suggest these elements as vehicles for delivery of G4 motifs in the introns of the bovine genes. Lastly, it seems that a basis exists for connecting traits of agricultural importance to the genetic variation of G4 motifs, thus, cattle could become an interesting new model organism for G4-related genetic studies.


2020 ◽  
Author(s):  
Yunzhong Wang ◽  
Saixing Tang ◽  
Yating Wen ◽  
Shuyuan Zheng ◽  
Bing Yang ◽  
...  

<div>Persistent room-temperature phosphorescence (p-RTP) from pure organics is attractive </div><div>due to its fundamental importance and potential applications in molecular imaging, </div><div>sensing, encryption, anticounterfeiting, etc.1-4 Recently, efforts have been also made in </div><div>obtaining color-tunable p-RTP in aromatic phosphors5 and nonconjugated polymers6,7. </div><div>The origin of color-tunable p-RTP and the rational design of such luminogens, </div><div>particularly those with explicit structure and molecular packing, remain challenging. </div><div>Noteworthily, nonconventional luminophores without significant conjugations generally </div><div>possess excitation-dependent photoluminescence (PL) because of the coexistence of </div><div>diverse clustered chromophores6,8, which strongly implicates the possibility to achieve </div><div>color-tunable p-RTP from their molecular crystals assisted by effective intermolecular </div><div>interactions. Here, inspirited by the highly stable double-helix structure and multiple </div><div>hydrogen bonds in DNA, we reported a series of nonconventional luminophores based on </div><div>hydantoin (HA), which demonstrate excitation-dependent PL and color-tunable p-RTP </div><div>from sky-blue to yellowish-green, accompanying unprecedentedly high PL and p-RTP </div><div>efficiencies of up to 87.5% and 21.8%, respectively. Meanwhile, the p-RTP emissions are </div><div>resistant to vigorous mechanical grinding, with lifetimes of up to 1.74 s. Such robust, </div><div>color-tunable and highly efficient p-RTP render the luminophores promising for varying </div><div>applications. These findings provide mechanism insights into the origin of color-tunable </div><div>p-RTP, and surely advance the exploitation of efficient nonconventional luminophores.</div>


2021 ◽  
Author(s):  
Anirban Ghosh ◽  
Eric Largy ◽  
Valérie Gabelica

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).


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.


2020 ◽  
Vol 48 (3) ◽  
pp. 1108-1119 ◽  
Author(s):  
Rajendra Kumar ◽  
Karam Chand ◽  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Snehasish Bhattacharjee ◽  
...  

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.


1972 ◽  
Vol 27 (2) ◽  
pp. 196-200 ◽  
Author(s):  
S. Marciani ◽  
M. Terbojevic ◽  
F. Dall’Acqua

Light scattering measurements performed on DNA after irradiation in the presence of psoralen clearly show that inter strand cross linkings are present in the macromolecule. In fact after heat denaturation and successive cooling irradiated macromolecule shows a molecular weight practically unchanged while a DNA sample after the same treatment shows a molecular weight half of the intact native DNA. Also the general conformation of irradiated DNA undergoes practically to no modifications after the same heat treatment while native DNA shows itself to have been strongly modified. Moreover, on the basis of flow dichroism determinations, DNA cross-linked by psoralen after heat denaturation showed to be able to restore its ordered double helix structure, during the successive cooling.


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