Review
Biochemistry & Molecular Biology
Nuria Escaja, Bartomeu Mir, Miguel Garavis, Carlos Gonzalez
Summary: Tetrads are arrangements of four nucleobases commonly used to stabilize nucleic acid structures. In addition to the well-known G-quadruplex, non-G tetrads formed by different nucleobases have been observed in experimental structures. They are mostly found in the context of G-quadruplex structures but also occur in other unusual four-stranded structures.
Article
Biochemistry & Molecular Biology
Marc Farag, Cedric Messaoudi, Liliane Mouawad
Summary: ASC-G4 is an algorithm that calculates the advanced structural characteristics of G-quadruplexes (G4). It determines the intramolecular G4 topology and resolves the ambiguity in guanine glycosidic configuration. The algorithm shows that using C3' or C5' atoms is more appropriate than P atoms for calculating groove width in G4, and that minimum groove width is a better measure of available space. ASC-G4 was applied to 207 G4 structures, guiding the calculations. The ASC-G4 website allows users to upload their G4 structures and obtain information on topology, loop types and lengths, snapbacks and bulges, guanine distribution, glycosidic configuration, groove widths, minimum groove widths, tilt and twist angles, backbone dihedral angles, and relevant atom-atom and atom-plane distances for structure evaluation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Vaclav Brazda, Natalia Bohalova, Richard P. Bowater
Summary: With improved sequencing methods, the new end-to-end assembly of human chromosome 8 has revealed a greater presence of non-B DNA structures than previously estimated, indicating their potential importance has been underestimated. As sequencing technologies continue to advance, similar discoveries may arise across the genomes of various organisms.
Article
Chemistry, Multidisciplinary
Haomiao Su, Jinglei Xu, Yuqi Chen, Qi Wang, Ziang Lu, Yage Chen, Kun Chen, Shaoqing Han, Zhentian Fang, Ping Wang, Bi-Feng Yuan, Xiang Zhou
Summary: This study reported a genome-wide strategy for identifying G4RPs and successfully identified a large number of G4RPs. Using this method, new G4 binding proteins were discovered, confirming the interaction of SERBP1 with G4. This developed a new strategy for studying the biological roles of nucleic secondary structures interacting with proteins in cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Tingting Zou, Yuka Sato, Shuma Kaneyoshi, Kota Mano, Rui Yasukawa, Yoshifumi Nakano, Satoshi Fujii, Shinobu Sato, Shigeori Takenaka
Summary: The newly synthesized NDI-beta-CyDs exhibit improved specificity for G-quadruplex structures, particularly the telomere RNA G-quadruplex. Beta-cyclodextrins in the complex may contribute to nucleobase inclusion.
Article
Biology
Shuntaro Takahashi, Sudipta Bhowmik, Shinobu Sato, Shigeori Takenaka, Naoki Sugimoto
Summary: The relationship between G4 structures and DNA replication was studied, and it was found that different ligands have different effects on the topology of G4. Some ligands can inhibit the replication of G4 with anti-parallel topology, while others selectively inhibit G4 with anti-parallel and hybrid topology. The experiments suggest that native human telomere G4 is more flexible than the modified sequence and can interact with ligands.
Article
Biochemistry & Molecular Biology
Ming Ye, Erin V. Chen, Shawn H. Pfeil, Kailey N. Martin, Tamanaa Atrafi, Sara Yun, Zahara Martinez, Liliya A. Yatsunyk
Summary: DNA can fold into G-quadruplexes (GQs), non-canonical secondary structures formed by pi-pi stacking of G-tet-rads. GQs are important in many biological processes, which makes them promising therapeutic targets. We investigated the role of adenines in GQ structure formation by performing biophysical and X-ray crystallographic studies of a purine-only G-rich sequence named GA1-5 and its complexes with GQ ligand N-methyl mesoporphyrin IX (NMM). The structures confirmed the parallel topology of GQs with loops formed by adenines and showed NMM binding at the 3' G-tetrad, contributing to our understanding of the structural diversity of GQs and their interactions with ligands.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wenxuan Hu, Haitao Jing, Wenqiang Fu, Zengrong Wang, Jiang Zhou, Na Zhang
Summary: In this study, a new type of G-quadruplex structure, parallel homomeric bimolecular G-quadruplex, was demonstrated to undergo strand displacement reaction with short G-rich DNA fragments at room temperature, resulting in the formation of a parallel heteromeric trimolecular G-quadruplex. This provides new insights into the development of complex architectures in G-quadruplex-based DNA nanotechnology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Yan Zhang, Zhidong Qiu, Ming Zhu, Ye Teng
Summary: Compound K (CK), a major metabolite of Panax ginseng, has been shown to enhance the formation of G-quadruplexes (G4s) and stabilize them through electrostatic interactions. This in turn, leads to the regulation of transcription involving G4-containing templates, resulting in reduced full-length transcripts and decreased transcription efficiency. These findings provide new insights into the pharmacological study of ginsenosides at the gene level.
Article
Biology
Besik Kankia
Summary: This article discusses the quadruplex world hypothesis, which provides an alternative explanation for the origin of life compared to the RNA world hypothesis. The hypothesis suggests that quadruplexes can initiate life without the need for complementarity and preexisting rules, through self-assembly and polymerization, and evolve step-by-step into extant biochemistry.
Article
Biochemistry & Molecular Biology
Dawei Li, Xiyu Chen, Rumeng Yan, Zeshan Jiang, Bing Zhou, Bei Lv
Summary: It was found that oligodeoxynucleotides (ODNs) containing G-quadruplexes can efficiently inhibit the activity of DNA topoisomerase I. Among them, the parallel propeller-type G-quadruplex is the most effective inhibitor. Combining G-quadruplexes with duplexes to form hybrids can enhance the inhibition efficiency. Moreover, a circular ODN with a G-quadruplex motif and DNA topoisomerase I binding site showed high inhibitory efficiency.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Valeria Libera, Federico Bianchi, Barbara Rossi, Francesco D'Amico, Claudio Masciovecchio, Caterina Petrillo, Francesco Sacchetti, Alessandro Paciaroni, Lucia Comez
Summary: This study found that during the thermal melting process of G4 structure, the hydrogen-bonded network of water molecules undergoes rearrangement, which is closely related to the DNA rearrangement. Understanding the structural properties of the solvent can contribute to a better understanding of the interaction between G4s and ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Valeria Libera, Elena A. Andreeva, Anne Martel, Aurelien Thureau, Marialucia Longo, Caterina Petrillo, Alessandro Paciaroni, Giorgio Schiro, Lucia Comez
Summary: This study employed a structure-based strategy to investigate the interaction between TMPyP4 porphyrin and a human telomeric sequence, revealing that porphyrin binding promotes dimerization and light irradiation can control the dimer fraction. Changes in quaternary structure were found to be closely correlated with modifications at the secondary structure level.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Microbiology
Elishiba Muturi, Fei Meng, Huan Liu, Mengwei Jiang, Hongping Wei, Hang Yang
Summary: The study found that functional PQSs in the ASFV genome, which can form stable G4s in the presence of K+ and be stabilized by G4 ligands such as NMM and PDS, could serve as potential targets for antiviral drugs. Experimental results showed that NMM and PDS can significantly suppress the expression of ASFV genes and inhibit the replication of ASFV in Porcine Alveolar Macrophages.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Poulomi Das, Fernaldo Richtia Winnerdy, Arijit Maity, Yves Mechulam, Anh Tuan Phan
Summary: A recent study identified a new motif involved in the formation of left-handed G-quadruplex DNA and determined the X-ray crystal structure of an LHG4 containing this motif. Structural analysis revealed the importance of split guanines and single thymine loops in promoting LHG4 formation.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Analytical
Yun Chen, Dehui Qiu, Xiaobo Zhang, Yuan Liu, Mingpan Cheng, Jianping Lei, Jean-Louis Mergny, Huangxian Ju, Jun Zhou
Summary: In this study, F3T-azaC-hemin, a G4-based construct, was designed to address the low activity issue of G-quadruplex/hemin (G4/hemin) DNAzymes. The performances of the G4-DNAzyme were significantly improved, resulting in a new and highly efficient molecular tool for ultrasensitive chemiluminescent detection of miRNA-221.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
David Moreira, Daniela Leitao, Jessica Lopes-Nunes, Tiago Santos, Joana Figueiredo, Andre Miranda, Daniela Alexandre, Candida Tomaz, Jean-Louis Mergny, Carla Cruz
Summary: In this study, the formation and stability of G-quadruplex structure of a G-rich DNA aptamer AT11-L2 were explored under different experimental conditions, along with its interactions with various G4 ligands and nucleolin (NCL). The results showed that AT11-L2 adopted different topologies depending on the KCl concentration, and the addition of ligands significantly stabilized the G-quadruplex structure. Furthermore, a specific interaction between AT11-L2 G-quadruplex and NCL was identified, and co-localization of these two molecules was observed in certain cell lines.
Article
Nanoscience & Nanotechnology
Xuanxiang Mao, Dehui Qiu, Shijiong Wei, Xiaobo Zhang, Jianping Lei, Jean-Louis Mergny, Huangxian Ju, Jun Zhou
Summary: This study reports a new dual-Hemin-G-quadruplex DNAzyme and its integration with glucose oxidase (GOx) within a hydrophilic metal-organic framework MAF-7 for a biocatalytic cascade system. The system shows high catalytic activity, good protective performance, and excellent recyclability, making it suitable for biosensing and industrial processes.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Yu Luo, Anton Granzhan, Julien Marquevielle, Anne Cucchiarini, Laurent Lacroix, Samir Amrane, Daniela Verga, Jean-Louis Mergny
Summary: Besides the DNA double-helix, G-quadruplexes are non-canonical nucleic acid structures that regulate crucial biological activities. This article provides an overview of G-quadruplexes and a detailed description of the biophysical and biochemical methods used to study them in vitro. The aim is to establish guidelines for standardized research on G-quadruplexes.
Article
Biochemistry & Molecular Biology
Samir Amrane, Chloe Jaubert, Amina Bedrat, Tiffany Rundstadler, Patricia Recordon-Pinson, Cindy Aknin, Aurore Guedin, Aurore De Rache, Laura Bartolucci, Ibra Diene, Frederic Lemoine, Olivier Gascuel, Genevieve Pratviel, Jean-Louis Mergny, Marie-Line Andreola
Summary: The formation of G-quadruplex structures during HIV-1 infection plays a crucial role in viral replication and processing of viral RNA genome. The use of G4-binders has shown to efficiently inhibit HIV-1 infectivity.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Genetics & Heredity
Soujanya Vinayagamurthy, Sulochana Bagri, Jean-Louis Mergny, Shantanu Chowdhury
Summary: Although the impact of telomeres on physiology is well established, the molecular mechanisms by which telomeres affect cellular functions remain unclear. Recent studies have identified telomere-binding factors with non-telomeric functions and discovered the prevalence of locally induced DNA secondary structures called G-quadruplexes in telomeres and gene regulatory regions. These findings suggest that telomeres may impact the non-telomeric genome through associations with factors that influence cell-intrinsic functions and have implications for aging, cancer, and pluripotency.
TRENDS IN GENETICS
(2023)
Review
Cell Biology
Lucille Ferret, Karla Alvarez-Valadez, Jennifer Riviere, Alexandra Muller, Natalia Bohalova, Luo Yu, Lionel Guittat, Vaclav Brazda, Guido Kroemer, Jean-Louis Mergny, Mojgan Djavaheri-Mergny
Summary: Guanine-quadruplex structures (G4) are formed by guanine-rich DNA and RNA sequences and control gene expression mechanisms. G4 ligands have been developed for potential therapeutic applications in human diseases. Recent evidence suggests that G4 ligands may target cellular components such as lysosomes and mitochondria.
Article
Oncology
Rongxin Zhang, Huiling Shu, Yuqi Wang, Tiantong Tao, Jing Tu, Cheng Wang, Jean-Louis Mergny, Xiao Sun
Summary: In this study, the relationship between G-quadruplexes (G4) and somatic structural variants (SV) in cancers was investigated using bioinformatic approaches and multiomics data. It was found that G4 regions were significantly enriched with somatic SV breakpoints, particularly at the boundary of topologically associated domains. G4 regions were also associated with earlier replication timing and open chromatin status. Machine learning models suggested G4 propensity as an important feature for predicting the density of SV breakpoints. These findings highlight the critical role of G4 structures in modulating the production of somatic SVs in cancers.
Article
Chemistry, Multidisciplinary
Xiaobo Zhang, Dehui Qiu, Jielin Chen, Yue Zhang, Jiawei Wang, Desheng Chen, Yuan Liu, Mingpan Cheng, David Monchaud, Jean-Louis Mergny, Huangxian Ju, Jun Zhou
Summary: Chimeric peptide-DNAzyme (CPDzyme) is a novel artificial peroxidase that assembles DNA, peptides, and an enzyme cofactor covalently in a single scaffold. The optimized CPDzyme prototype G4-Hemin-KHRRH is >2000-fold more active than the non-covalent G4/Hemin complex and >1.5-fold more active than the native peroxidase. The precise selection and arrangement of CPDzyme components enable synergistic interactions and wide range applications under non-physiological conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Petra Skolakova, Martin Gajarsky, Jan Palacky, Denis Subert, Daniel Renciuk, Lukas Trantirek, Jean-Louis Mergny, Michaela Vorlickova
Summary: Based on various techniques, this study demonstrates that Cytosine-rich DNA regions can form four-stranded structures called i-motifs (iMs) under neutral or slightly alkaline conditions. These iMs exhibit long-lasting kinetics and melt with significant hysteresis. Furthermore, the presence of different iM species, the proportion of which is dependent on temperature and incubation time, is observed in sequences with a length greater than 6.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Csaba Papp, Vineeth T. Mukundan, Piroon Jenjaroenpun, Fernaldo Richtia Winnerdy, Ghim Siong Ow, Anh Tuan Phan, Vladimir A. Kuznetsov
Summary: The composition of DNA sequences determines the structure and stability of G-quadruplexes (G4s). In this study, a large family of computationally defined and experimentally verified potential G4-B forming sequences (pG4-BS) was introduced. These sequences are preferentially localized in transcription regulatory regions and are associated with brain tissue, immune, and developmental processes. The ability of these sequences to form G4 structures was predicted with 91.5% accuracy in vitro.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Vaclav Brazda, Michaela Dobrovolna, Natalia Bohalova, Jean-Louis Mergny
Summary: Hepatitis B virus (HBV) is a dangerous human pathogenic virus that has existed alongside humanity for thousands of years. Through analyzing modern and ancient HBV genomes, it was found that G-quadruplex-forming sequences (PQS) were present in all tested HBV genomes. The frequency of PQS in modern HBV genomes has increased over time and is approaching the frequency in the human genome. These results suggest a convergent evolution of PQS frequencies in chronic viral infections to mimic the host and avoid recognition as foreign material.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Physical
Dehui Qiu, Mingpan Cheng, Petr Stadlbauer, Jielin Chen, Michal Langer, Xiaobo Zhang, Qiang Gao, Huangxian Ju, Jiri Sponer, Jean-Louis Mergny, David Monchaud, Jun Zhou
Summary: The active sites of natural and artificial enzymes play a crucial role in their catalytic performance. This study focuses on G-quadruplex (GQ)/hemin DNAzymes and investigates how their active sites can be controlled and manipulated. Experimental and molecular dynamics simulation results reveal that the topology of the GQ and the flanking nucleotides influence the activation of hemin, providing valuable insights into the biocatalytic activity of GQs.
Article
Biochemistry & Molecular Biology
Yu Luo, Martina Lenarcic Zivkovic, Jiawei Wang, Jan Rynes, Silvie Foldynova-Trantirkova, Lukas Trantirek, Daniela Verga, Jean-Louis Mergny
Summary: Metal ions are essential for the survival of living organisms. The structures of G/C-rich sequences are influenced by the [Na+]/[K+] ratio, which can lead to the formation of competing structures.
NUCLEIC ACIDS RESEARCH
(2023)
