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Recent Advances in Non-Canonical Nucleic Acid Structures

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A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 27532

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Special Issue Editors

Dr. Liliya Yatsunyk

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Guest Editor

Department of Chemistry and Biochemistry, Swarthmore College, 500 College Avenue, Swarthmore, PA 19081, USA
Interests: G-quadruplex DNA; non-canonical DNA structures; ligands; porphyrins; spectroscopy; X-ray crystallography

Dr. David Monchaud

E-Mail Website
Guest Editor

Institut de Chimie Moléculaire, ICMUB CNRS UMR6302, UBFC, Dijon, France
Interests: DNA/RNA-quadruplexes, smart probes, sequencing, DNA junctions, ligands

Special Issue Information

Dear Colleagues,

The nucleic acids field is moving at an incredible pace, experiencing an unprecedented paradigm shift away from static, carved-in-stone concepts, e.g., the double helix of DNA is a complex database of genetic information waiting to be scanned according to the cellular activity (the "book of life"); or the many RNA found in cells, when not transcriptional noise, mostly act as molecular messengers abiding by the laws of the genetic code. In the current far more dynamic view, the cellular functions of both DNA and RNA rely not only on their sequences but also, and above all, on their tertiary structures, which are diverse (two-, three-, four-stranded architectures), dynamic (moulded by chaperone proteins, unfolded by resolving enzymes), and involved in intricate cellular regulation networks (with a remarkably broad spectrum of biological processes, from gene expression to genome maintenance). In this Special Issue, we wish to provide a snapshot of the current state of the field, focusing on the structural characterization of DNA, RNA, and DNA/RNA non-canonical structures (e.g., G-quadruplexes, i-motifs, three-way DNA junctions), novel methodologies to assess their existence and functional relevance in human cells (e.g., next generation sequencing, optical detection methods), as well as the strategies implemented to gain control over the key cellular events controlled by the non-canonical nucleic acid structures using ever more accurate and versatile molecular tools.

Dr. Liliya Yatsunyk
Dr. David Monchaud
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Non-canonical DNA/RNA structures (G-quadruplex, i-motif, triplex, three-way junctions)
Structural characterization (e.g. NMR, X-ray crystallographic analyses)
Biophysics/biochemical investigations (e.g., FRET, CD, PAGE, fluorescence analyses)
Cell biology (e.g., genetic regulatory networks, transcription/translation controls)
Non-canonical nucleic acid-binding partners (e.g., small-molecule ligands, proteins)
Bioinformatics, next-generation sequencing, genome-/transcriptome-wide analyses

Published Papers (4 papers)

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Research

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14 pages, 1882 KiB

Open AccessArticle

p53 Binds Preferentially to Non-B DNA Structures Formed by the Pyrimidine-Rich Strands of GAA·TTC Trinucleotide Repeats Associated with Friedreich’s Ataxia

by Robert Helma, Pavla Bažantová, Marek Petr, Matej Adámik, Daniel Renčiuk, Vlastimil Tichý, Alena Pastuchová, Zuzana Soldánová, Petr Pečinka, Richard P. Bowater, Miroslav Fojta and Marie Brázdová

Molecules 2019, 24(11), 2078; https://doi.org/10.3390/molecules24112078 - 31 May 2019

Cited by 5 | Viewed by 3366

Abstract

Expansions of trinucleotide repeats (TNRs) are associated with genetic disorders such as Friedreich’s ataxia. The tumor suppressor p53 is a central regulator of cell fate in response to different types of insults. Sequence and structure-selective modes of DNA recognition are among the main attributes of p53 protein. The focus of this work was analysis of the p53 structure-selective recognition of TNRs associated with human neurodegenerative diseases. Here, we studied binding of full length p53 and several deletion variants to TNRs folded into DNA hairpins or loops. We demonstrate that p53 binds to all studied non-B DNA structures, with a preference for non-B DNA structures formed by pyrimidine (Py) rich strands. Using deletion mutants, we determined the C-terminal DNA binding domain of p53 to be crucial for recognition of such non-B DNA structures. We also observed that p53 in vitro prefers binding to the Py-rich strand over the purine (Pu) rich strand in non-B DNA substrates formed by sequence derived from the first intron of the frataxin gene. The binding of p53 to this region was confirmed using chromatin immunoprecipitation in human Friedreich’s ataxia fibroblast and adenocarcinoma cells. Altogether these observations provide further evidence that p53 binds to TNRs’ non-B DNA structures. Full article

(This article belongs to the Special Issue Recent Advances in Non-Canonical Nucleic Acid Structures)

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10 pages, 1245 KiB

Open AccessArticle

Impact of Small Molecules on Intermolecular G-Quadruplex Formation

by Prabesh Gyawali, Keshav GC, Yue Ma, Sanjaya Abeysirigunawardena, Kazuo Nagasawa and Hamza Balci

Molecules 2019, 24(8), 1570; https://doi.org/10.3390/molecules24081570 - 20 Apr 2019

Cited by 4 | Viewed by 4362

Abstract

We performed single molecule studies to investigate the impact of several prominent small molecules (the oxazole telomestatin derivative L2H2-6OTD, pyridostatin, and Phen-DC₃) on intermolecular G-quadruplex (i-GQ) formation between two guanine-rich DNA strands that had 3-GGG repeats in one strand and 1-GGG repeat in the other (3+1 GGG), or 2-GGG repeats in each strand (2+2 GGG). Such structures are not only physiologically significant but have recently found use in various biotechnology applications, ranging from DNA-based wires to chemical sensors. Understanding the extent of stability imparted by small molecules on i-GQ structures, has implications for these applications. The small molecules resulted in different levels of enhancement in i-GQ formation, depending on the small molecule and arrangement of GGG repeats. The largest enhancement we observed was in the 3+1 GGG arrangement, where i-GQ formation increased by an order of magnitude, in the presence of L2H2-6OTD. On the other hand, the enhancement was limited to three-fold with Pyridostatin (PDS) or less for the other small molecules in the 2+2 GGG repeat case. By demonstrating detection of i-GQ formation at the single molecule level, our studies illustrate the feasibility to develop more sensitive sensors that could operate with limited quantities of materials. Full article

(This article belongs to the Special Issue Recent Advances in Non-Canonical Nucleic Acid Structures)

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Review

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18 pages, 6232 KiB

Open AccessFeature PaperReview

ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1

by Kenneth I. Onyedibe, Modi Wang and Herman O. Sintim

Molecules 2019, 24(22), 4192; https://doi.org/10.3390/molecules24224192 - 19 Nov 2019

Cited by 60 | Viewed by 12161

Abstract

Ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodiesterase that degrades the stimulator of interferon genes (STING) ligand, cyclic GMP–AMP (cGAMP). cGAMP or analogs thereof have emerged as potent immunostimulatory agents, which have potential applications in immunotherapy. This emerging role of ENPP1 has placed this “old” enzyme at the frontier of immunotherapy. This review highlights the roles played by ENPP1, the mechanism of cGAMP hydrolysis by ENPP1, and small molecule inhibitors of ENPP1 with potential applications in diverse disease states, including cancer. Full article

(This article belongs to the Special Issue Recent Advances in Non-Canonical Nucleic Acid Structures)

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Graphical abstract

15 pages, 1617 KiB

Open AccessReview

Mechanisms of DNA Replication and Repair: Insights from the Study of G-Quadruplexes

by Tracy M. Bryan

Molecules 2019, 24(19), 3439; https://doi.org/10.3390/molecules24193439 - 22 Sep 2019

Cited by 57 | Viewed by 6871

Abstract

G-quadruplexes are four-stranded guanine-rich structures that have been demonstrated to occur across the genome in humans and other organisms. They provide regulatory functions during transcription, translation and immunoglobulin gene rearrangement, but there is also a large amount of evidence that they can present a potent barrier to the DNA replication machinery. This mini-review will summarize recent advances in understanding the many strategies nature has evolved to overcome G-quadruplex-mediated replication blockage, including removal of the structure by helicases or nucleases, or circumventing the deleterious effects on the genome through homologous recombination, alternative end-joining or synthesis re-priming. Paradoxically, G-quadruplexes have also recently been demonstrated to provide a positive role in stimulating the initiation of DNA replication. These recent studies have not only illuminated the many roles and consequences of G-quadruplexes, but have also provided fundamental insights into the general mechanisms of DNA replication and its links with genetic and epigenetic stability. Full article

(This article belongs to the Special Issue Recent Advances in Non-Canonical Nucleic Acid Structures)

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