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The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 December 2021) | Viewed by 34727

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Special Issue Editors

Dr. Aldo Galeone

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Department of Pharmacy, Università degli Studi di Napoli Federico II, Naples, Italy
Interests: G-quadruplex; nucleic acid secondary structures; aptamers; nucleic acid chemistry
Special Issues, Collections and Topics in MDPI journals

Dr. Veronica Esposito

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Department of Pharmacy, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Interests: G-quadruplex; aptamers; nucleic acid chemistry; nuclear magnetic resonance; molecular modelling; circular dichroism
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Dr. Antonella Virgilio

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Guest Editor

Department of Pharmacy, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Interests: G-quadruplex; aptamers; nucleic acid chemistry; circular dichroism; electrophoresis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

G-quadruplex structures are secondary conformations of nucleic acids, whose constitutive unit is the G-tetrad or G-quartet. This building block consists of a square planar arrangement of four guanosines, in which each base is associated to the adjacent ones through four hydrogen bonds. The stacking of two or more G-tetrad units can form larger and more stable structures. The occurrance of monovalent cations, between two adjacent G-tetrads or also in the center of a G-tetrad, further contributes to the structural stability of the G-quadruplex complexes. The biological significance of these DNA or RNA structures is witnessed by their occurrence or potential formation in several regions of the human genome, such as telomeres, genes promoters, and transcription start sites. Furthermore, they can be involved in the regulation of gene expression and telomere maintenance. However, the importance of the G-quadruplex structures is not confined to genetics and molecular biological research. In fact, thanks to their remarkable stability and outstanding variability, these structures constitute the scaffolds of several DNA or RNA aptamers, with important applications in pharmaceutics, analytics, and diagnostics. Furthermore, suitable G-quadruplexes are also endowed with catalytic properties. Moreover, considering their self-assembly properties, G-quadruplexes are often exploited in building nanostructures and in developing nanodevices.

This Special Issue will concern a selection of original research, review articles, and commentaries focused on diverse topics, with particular attention on the relationship between the structural features of the G-quadruplexes and their functional role.

Dr. Aldo Galeone
Dr. Veronica Esposito
Dr. Antonella Virgilio
Guest Editors

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Keywords

G-quadruplex thermodynamics
G-quadruplex CD and fluorescence spectroscopy
G-quadruplex synthesis
G-quadruplex properties
G-quadruplex structure
G-quadruplex dynamics
G-quadruplex folding
G-quadruplex biological functions
G-quadruplex aptamers
G-quadruplex as a therapeutic target
Catalytic G-quadruplexes

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The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity in International Journal of Molecular Sciences (10 articles)

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16 pages, 4303 KiB

Open AccessArticle

Spectroscopic Characterization of Mitochondrial G-Quadruplexes

by Sara Illodo, Cibrán Pérez-González, Ramiro Barcia, Flor Rodríguez-Prieto, Wajih Al-Soufi and Mercedes Novo

Int. J. Mol. Sci. 2022, 23(2), 925; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020925 - 15 Jan 2022

Viewed by 2196

Abstract

Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication. In this study, we decipher the most relevant G4 structures that can be formed within CSB II: RNA G4 at the RNA transcript, DNA G4 within the non-transcribed strand and DNA:RNA hybrid between the RNA transcript and the non-transcribed strand. We show that the more abundant, but unexplored, G6AG7 (37%) and G6AG8 (35%) sequences in CSB II yield more stable G4s than the less profuse G5AG7 sequence. Moreover, the existence of a guanine located 1 bp upstream promotes G4 formation. In all cases, parallel G4s are formed, but their topology changes from a less ordered to a highly ordered G4 when adding small amounts of potassium or sodium cations. Circular dichroism was used due to discriminate different conformations and topologies of nucleic acids and was complemented with gel electrophoresis and fluorescence spectroscopy studies. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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12 pages, 1673 KiB

Open AccessArticle

Detection of CpG Methylation in G-Quadruplex Forming Sequences Using G-Quadruplex Ligands

by Hijiri Hasegawa, Ikkei Sasaki, Kaori Tsukakoshi, Yue Ma, Kazuo Nagasawa, Shusuke Numata, Yuuki Inoue, Yeji Kim and Kazunori Ikebukuro

Int. J. Mol. Sci. 2021, 22(23), 13159; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313159 - 06 Dec 2021

Cited by 2 | Viewed by 2563

Abstract

Genomic DNA methylation is involved in many diseases and is expected to be a specific biomarker for even the pre-symptomatic diagnosis of many diseases. Thus, a rapid and inexpensive detection method is required for disease diagnosis. We have previously reported that cytosine methylation in G-quadruplex (G4)-forming oligonucleotides develops different G4 topologies. In this study, we developed a method for detecting CpG methylation in G4-forming oligonucleotides based on the structural differences between methylated and unmethylated G4 DNAs. The differences in G4 topologies due to CpG methylation can be discriminated by G4 ligands. We performed a binding assay between methylated or unmethylated G4 DNAs and G4 ligands. The binding abilities of fluorescent G4 ligands to BCL-2, HRAS1, HRAS2, VEGF G4-forming sequences were examined by fluorescence-based microtiter plate assay. The differences in fluorescence intensities between methylated and unmethylated G4 DNAs were statistically significant. In addition to fluorescence detection, the binding of G4 ligand to DNA was detected by chemiluminescence. A significant difference was also detected in chemiluminescence intensity between methylated and unmethylated DNA. This is the first study on the detection of CpG methylation in G4 structures, focusing on structural changes using G4 ligands. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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20 pages, 5442 KiB

Open AccessArticle

DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures

by Chiara Platella, Rosa Gaglione, Ettore Napolitano, Angela Arciello, Valentina Pirota, Filippo Doria, Domenica Musumeci and Daniela Montesarchio

Int. J. Mol. Sci. 2021, 22(19), 10624; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910624 - 30 Sep 2021

Cited by 8 | Viewed by 1619

Abstract

G-quadruplex existence was proved in cells by using both antibodies and small molecule fluorescent probes. However, the G-quadruplex probes designed thus far are structure- but not conformation-specific. Recently, a core-extended naphthalene diimide (c_ex-NDI) was designed and found to provide fluorescent signals of markedly different intensities when bound to G-quadruplexes of different conformations or duplexes. Aiming at evaluating how the fluorescence behaviour of this compound is associated with specific binding modes to the different DNA targets, c_ex-NDI was here studied in its interaction with hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex models by biophysical techniques, molecular docking, and biological assays. c_ex-NDI showed different binding modes associated with different amounts of stacking interactions with the three DNA targets. The preferential binding sites were the groove, outer quartet, or intercalative site of the hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex, respectively. Interestingly, our data show that the fluorescence intensity of DNA-bound c_ex-NDI correlates with the amount of stacking interactions formed by the ligand with each DNA target, thus providing the rationale behind the conformation-sensitive properties of c_ex-NDI and supporting its use as a fluorescent probe of G-quadruplex structures. Notably, biological assays proved that c_ex-NDI mainly localizes in the G-quadruplex-rich nuclei of cancer cells. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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13 pages, 3881 KiB

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Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region

by Sabrina Dallavalle, Salvatore Princiotto, Luce M. Mattio, Roberto Artali, Loana Musso, Anna Aviñó, Ramon Eritja, Claudio Pisano, Raimundo Gargallo and Stefania Mazzini

Int. J. Mol. Sci. 2021, 22(16), 8737; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168737 - 14 Aug 2021

Cited by 4 | Viewed by 2177

Abstract

DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. These results open the possibility of exploring the development of better G-quadruplex binders that, in turn, may also inhibit the enzyme. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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9 pages, 1377 KiB

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Thrombin-Binding Aptamer with Inversion of Polarity Sites (IPS): Effect on DNAzyme Activity and Anticoagulant Properties

by Joanna Kosman and Bernard Juskowiak

Int. J. Mol. Sci. 2021, 22(15), 7902; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157902 - 23 Jul 2021

Cited by 3 | Viewed by 1579

Abstract

In this work we examined the properties of thrombin-binding aptamer (TBA) modified by the introduction of inversion of polarity sites (IPS) in order to assess the effect of modification on the activation of TBA to serve as DNAzyme with peroxidase-like activity. Two oligonucleotides were designed to possess one (IPS1) or three (IPS2) inversion sites. TBA typically forms antiparallel G-quadruplexes with two G-tetrads, which exhibits very low DNAzyme peroxidise activity. DNAzyme activity is generally attributed to parallel G-quadruplexes. Hence, inversion of polarity was introduced in the TBA molecule to force the change of G-quadruplex topology. All oligonucleotides were characterized using circular dichroism and UV-Vis melting profiles. Next, the activity of the DNAzymes formed by studied oligonucleotides and hemin was investigated. The enhancement of peroxidase activity was observed when inversion of polarity was introduced. DNAzyme based on IPS2 showed the highest peroxidase activity in the presence of K⁺ or NH₄⁺ ions. This proves that inversion of polarity can be used to convert a low-activity DNAzyme into a DNAzyme with high activity. Since TBA is known for its anticoagulant properties, the relevant experiments with IPS1 and IPS2 oligonucleotides were performed. Both IPS1 and IPS2 retain some anticoagulant activity in comparison to TBA in the reaction with fibrinogen. Additionally, the introduction of inversion of polarity makes these oligonucleotides more resistant to nucleases. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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14 pages, 4507 KiB

Open AccessArticle

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG₂T(G₃T)₃] and Its Derivatives with an Abasic Site Replacing Single Thymidine

by Antonella Virgilio, Daniela Benigno, Annalisa Pecoraro, Annapina Russo, Giulia Russo, Veronica Esposito and Aldo Galeone

Int. J. Mol. Sci. 2021, 22(13), 7040; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137040 - 30 Jun 2021

Cited by 8 | Viewed by 1657

Abstract

In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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18 pages, 16277 KiB

Open AccessArticle

G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides

by Carolina Roxo, Weronika Kotkowiak and Anna Pasternak

Int. J. Mol. Sci. 2021, 22(9), 4941; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094941 - 06 May 2021

Cited by 13 | Viewed by 2885

Abstract

G-quadruplexes (G4s) are non-canonical structures formed by guanine-rich sequences of DNA or RNA that have attracted increased attention as anticancer agents. This systematic study aimed to investigate the anticancer potential of five G4-forming, sequence-related DNA molecules in terms of their thermodynamic and structural properties, biostability and cellular uptake. The antiproliferative studies revealed that less thermodynamically stable G4s with three G-tetrads in the core and longer loops are more predisposed to effectively inhibit cancer cell growth. By contrast, highly structured G4s with an extended core containing four G-tetrads and longer loops are characterized by more efficient cellular uptake and improved biostability. Various analyses have indicated that the G4 structural elements are intrinsic to the biological activity of these molecules. Importantly, the structural requirements are different for efficient cancer cell line inhibition and favorable G4 cellular uptake. Thus, the ultimate antiproliferative potential of G4s is a net result of the specific balance among the structural features that are favorable for efficient uptake and those that increase the inhibitory activity of the studied molecules. Understanding the G4 structural features and their role in the biological activity of G-rich molecules might facilitate the development of novel, more potent G4-based therapeutics with unprecedented anticancer properties. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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12 pages, 2499 KiB

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Supramolecular Polymorphism of (G₄C₂)_n Repeats Associated with ALS and FTD

by Melani Potrč, Nerea Sebastián, Miha Škarabot, Irena Drevenšek-Olenik and Lea Spindler

Int. J. Mol. Sci. 2021, 22(9), 4532; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094532 - 26 Apr 2021

Cited by 3 | Viewed by 2347

Abstract

Guanine-rich DNA sequences self-assemble into highly stable fourfold structures known as DNA-quadruplexes (or G-quadruplexes). G-quadruplexes have furthermore the tendency to associate into one-dimensional supramolecular aggregates termed G-wires. We studied the formation of G-wires in solutions of the sequences d(G₄C₂)_n with n = 1, 2, and 4. The d(G₄C₂)_n repeats, which are associated with some fatal neurological disorders, especially amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), represent a challenging research topic due to their extensive structural polymorphism. We used dynamic light scattering (DLS) to measure translational diffusion coefficients and consequently resolve the length of the larger aggregates formed in solution. We found that all three sequences assemble into longer structures than previously reported. The d(G₄C₂) formed extremely long G-wires with lengths beyond 80 nm. The d(G₄C₂)₂ formed a relatively short stacked dimeric quadruplex, while d(G₄C₂)₄ formed multimers corresponding to seven stacked intramolecular quadruplexes. Profound differences between the multimerization properties of the investigated sequences were also confirmed by the AFM imaging of surface films. We propose that π-π stacking of the basic G-quadruplex units plays a vital role in the multimerization mechanism, which might be relevant for transformation from the regular medium-length to disease-related long d(G₄C₂)_n repeats. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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14 pages, 2277 KiB

Open AccessArticle

The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus

by Anastasia A. Bizyaeva, Dmitry A. Bunin, Valeria L. Moiseenko, Alexandra S. Gambaryan, Sonja Balk, Vadim N. Tashlitsky, Alexander M. Arutyunyan, Alexey M. Kopylov and Elena G. Zavyalova

Int. J. Mol. Sci. 2021, 22(5), 2409; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052409 - 27 Feb 2021

Cited by 10 | Viewed by 3462

Abstract

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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14 pages, 2783 KiB

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Aptamers Against the β-Conglutin Allergen: Insights into the Behavior of the Shortest Multimeric(Intra)Molecular DNA G-Quadruplex

by Ciara K. O’ Sullivan, Teresa Mairal, Miriam Jauset-Rubio, Marketa Svobodova, Vasso Skouridou, Veronica Esposito, Antonella Virgilio and Aldo Galeone

Int. J. Mol. Sci. 2021, 22(3), 1150; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031150 - 24 Jan 2021

Cited by 6 | Viewed by 2313

Abstract

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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13 pages, 2489 KiB

Open AccessArticle

Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter

by Annalisa Ferino and Luigi E. Xodo

Int. J. Mol. Sci. 2021, 22(3), 1137; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031137 - 24 Jan 2021

Cited by 4 | Viewed by 2165

Abstract

The promoter of the Kirsten ras (KRAS) proto-oncogene contains, upstream of the transcription start site, a quadruplex-forming motif called 32R with regulatory functions. As guanine under oxidative stress can be oxidized to 8-oxoguanine (8OG), we investigated the capacity of glycosylases 8-oxoguanine glycosylase (OGG1) and endonuclease VIII-like 1 (Neil1) to excise 8OG from 32R, either in duplex or G-quadruplex (G4) conformation. We found that OGG1 efficiently excised 8OG from oxidized 32R in duplex but not in G4 conformation. By contrast, glycosylase Neil1 showed more activity on the G4 than the duplex conformation. We also found that the excising activity of Neil1 on folded 32R depended on G4 topology. Our data suggest that Neil1, besides being involved in base excision repair pathway (BER), could play a role on KRAS transcription. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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Review

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14 pages, 603 KiB

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The Dynamic Regulation of G-Quadruplex DNA Structures by Cytosine Methylation

by Aaron John Stevens, Lucy de Jong and Martin Alexander Kennedy

Int. J. Mol. Sci. 2022, 23(5), 2407; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052407 - 22 Feb 2022

Cited by 7 | Viewed by 4983

Abstract

It is well known that certain non B-DNA structures, including G-quadruplexes, are key elements that can regulate gene expression. Here, we explore the theory that DNA modifications, such as methylation of cytosine, could act as a dynamic switch by promoting or alleviating the structural formation of G-quadruplex structures in DNA or RNA. The interaction between epigenetic DNA modifications, G4 formation, and the 3D architecture of the genome is a complex and developing area of research. Although there is growing evidence for such interactions, a great deal still remains to be discovered. In vivo, the potential effect that cytosine methylation may have on the formation of DNA structures has remained largely unresearched, despite this being a potential mechanism through which epigenetic factors could regulate gene activity. Such interactions could represent novel mechanisms for important biological functions, including altering nucleosome positioning or regulation of gene expression. Furthermore, promotion of strand-specific G-quadruplex formation in differentially methylated genes could have a dynamic role in directing X-inactivation or the control of imprinting, and would be a worthwhile focus for future research. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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21 pages, 3470 KiB

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The Relevance of G-Quadruplexes for DNA Repair

by Rebecca Linke, Michaela Limmer, Stefan A. Juranek, Annkristin Heine and Katrin Paeschke

Int. J. Mol. Sci. 2021, 22(22), 12599; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212599 - 22 Nov 2021

Cited by 27 | Viewed by 3377

Abstract

DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events. G-quadruplex-driven genome instability is connected to tumorigenesis and other genetic disorders. In recent years, the connection between genome stability, DNA repair and G4 formation was further underlined by the identification of multiple DNA repair proteins and ligands which bind and stabilize said G4 structures to block specific DNA repair pathways. The relevance of G4s for different DNA repair pathways is complex and depends on the repair pathway itself. G4 structures can induce DNA damage and block efficient DNA repair, but they can also support the activity and function of certain repair pathways. In this review, we highlight the roles and consequences of G4 DNA structures for DNA repair initiation, processing, and the efficiency of various DNA repair pathways. Full article

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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