Article
Biochemistry & Molecular Biology
Ying Ma, Yang Yang, Jingyu Xin, Lingfeng He, Zhigang Hu, Tao Gao, Feiyan Pan, Zhigang Guo
Summary: Reactive oxygen species (ROS) are highly oxidative molecules that induce DNA damage and affect gene expression. This study identified a novel RNA G-quadruplex (rG4) sequence in the 5' untranslated region (5' UTR) of FEN1 mRNA. Under oxidative stress, ROS can oxidize the G bases in the G4-forming sequence, disrupting the structure of G-quadruplex. Additionally, a novel rG4-binding protein hnRNPA1 was identified and shown to play a role in regulating FEN1 expression. Overall, this study reveals a novel role for rG4 in translational control under oxidative stress.
Review
Chemistry, Medicinal
Francesca Romano, Anna Di Porzio, Nunzia Iaccarino, Gelsomina Riccardi, Ritamaria Di Lorenzo, Sonia Laneri, Bruno Pagano, Jussara Amato, Antonio Randazzo
Summary: Modulation of G-quadruplex (G4) formation has been proposed as a powerful tool for cancer treatment through the control of oncogene expression. This review provides an overview of current knowledge on G4s in human oncogene promoters and the most representative G4-binding ligands. Targeting G4s has the potential to develop novel and highly specific anticancer drugs capable of selectively impacting gene expression.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Review
Chemistry, Multidisciplinary
Robert C. Monsen
Summary: G-quadruplexes (G4s) are secondary structures in nucleic acids formed in guanine-rich regions. They are abundant in the genome, especially in gene promoter regions. G4s function as epigenetic features and binding centers for transcription factors. Stabilizing or disrupting G4s in gene promoters directly affects adjacent gene transcription, making them potential drug targets for hard-to-target proteins in cancer. However, the lack of distinctive receptor structures and off-target effects have hindered the progress of G4 ligands in clinical trials. This review suggests shifting the focus to higher-order G4 structures as selective molecular targets.
FRONTIERS IN CHEMISTRY
(2023)
Review
Genetics & Heredity
MaryElizabeth Stein, Kristin A. Eckert
Summary: Genome instability, especially in cancer cells, is associated with DNA structures like G-quadruplexes and oxidative damage caused by chronic inflammation. Maintaining stability in the genome requires specialized DNA polymerases to handle challenges posed by G4 structures and unrepaired lesions from inflammation. Inflammation's impact on gene regulation and mutagenesis through G4 structures requires further investigation for a better understanding of genome instability mechanisms.
Article
Pharmacology & Pharmacy
Rosario Amato, Maria Grazia Rossino, Maurizio Cammalleri, Anna Maria Timperio, Giuseppina Fanelli, Massimo Dal Monte, Laura Pucci, Giovanni Casini
Summary: Research demonstrates that LG can protect the retina from oxidative stress, inflammation, apoptosis, and other damages, as well as exert protective effects in a glaucoma model. LG treatment improved RGC function, reduced oxidative stress and inflammation markers, decreased RGC loss and glial cell activation. Additionally, LG components were found in the retina.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mingxin Ye, Hui Li, Hongjun Luo, Yongyin Zhou, Wenhong Luo, Zhexuan Lin
Summary: This study found that erythrocytes metabolize methionine to homocysteine, which enhances the antioxidative capability of erythrocytes and protects them against damage from reactive oxygen species.
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
Microbiology
Galina V. Chashchina, Anna K. Shchyolkina, Simon V. Kolosov, Artemy D. Beniaminov, Dmitry N. Kaluzhny
Summary: Evolutionary conservation or over-representation of potential G-quadruplex sequences (PQS) in genomes are often seen as functional indicators; however, uneven base distribution may lead to an apparent abundance of PQS over average. Analysis of archaeal genomes revealed multiple interspersed highly similar PQSs in Methanomicrobiaceae family, which could form G-quadruplex (G4) structure in the presence of potassium ions. Furthermore, a cytosine-rich track adjacent to the 3'-end of each rPQS was found to influence the formation of alternative DNA structures depending on potassium ion presence.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Plant Sciences
Isabel P. Pais, Rita Moreira, Jose N. Semedo, Jose C. Ramalho, Fernando C. Lidon, Jose Coutinho, Benvindo Macas, Paula Scotti-Campos
Summary: Inundation, excessive precipitation, or inadequate field drainage can lead to waterlogging of cultivated land. Climate change is expected to increase flooding events, which affects wheat production and leads to yield losses. Understanding changes in soil and plant physiology under excess water conditions is crucial due to the importance of wheat as a major food source.
Article
Virology
Lu Lv, Leiliang Zhang
Summary: Monkeypox virus (MPXV), a member of Orthopoxvirus, has caused a Public Health Emergency of International Concern with a significant increase in cases and geographic range in 2022. This study aims to characterize the G-quadruplex (GQ) secondary structures encoded by MPXV and evaluate the binding and stabilization abilities of GQ ligands. The results demonstrate the presence of MPXV GQ and suggest GQs could be potential antiviral targets, providing a new approach for MPXV therapy.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Chemistry, Multidisciplinary
Luying Chen, Jonathan Dickerhoff, Saburo Sakai, Danzhou Yang
Summary: DNA G-quadruplexes formed in human telomeres and oncogene promoters are functionally important and have emerged as a promising class of cancer-specific drug targets. In this article, the authors discuss their efforts to understand the structures and functions of these DNA G-quadruplexes and their interactions with small molecules. They have determined the high-resolution structures of telomeric G-quadruplexes and studied G-quadruplexes formed in key oncogene promoters. The authors also highlight the potential of G-quadruplexes as selectively targetable drug receptors and discuss their recent discoveries of small molecules that specifically recognize these G-quadruplexes. Overall, this work provides a strong foundation for future research on G-quadruplexes and the design of G-quadruplex-targeted drugs.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Andrea P. Falanga, Monica Terracciano, Giorgia Oliviero, Giovanni N. Roviello, Nicola Borbone
Summary: G-quadruplex (G4) structures in plants have significant implications in biological processes and pathological states. The exploration of plant compounds and G4 ligands can lead to potential anticancer treatments and biomedical applications.
Article
Biochemistry & Molecular Biology
Nirali Pandya, Mamta Singh, Reshma Rani, Vinit Kumar, Amit Kumar
Summary: Small molecule BiGh binds to bcl-2 G4 DNA structure with high affinity and selectivity, stabilizes the G4 motif, down-regulates bcl-2 gene transcription, induces cell apoptosis, and exhibits potential anti-cancer activity. This work provides a potential platform for the development of G4 stabilizers with drug-like properties.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Laboni Roy, Ananya Roy, Debopriya Bose, Nilanjan Banerjee, Subhrangsu Chatterjee
Summary: A 25 nt G-rich sequence in the promoter region of SMO oncogene was identified to form a parallel G quadruplex (SMO1-GQ). SMO1-GQ is highly conserved in primates. In-depth studies using spectroscopic and computational analysis revealed a stable interaction between SMO1-GQ and the small molecule BRACO-19. Further experiments showed that SMO1-GQ functions as a scaffold for multiple transcription factors and may serve as a promising target for anti-cancer drug development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Giulia Nicoletto, Sara N. Richter, Ilaria Frasson
Summary: This study reports the presence, conservation, and localization of putative G4-forming sequences (PQSs) in human arboviruses. Analysis revealed that positive-strand ssRNA arboviruses, especially Flaviviruses, are enriched in highly conserved PQSs located in coding sequences (CDSs) or untranslated regions (UTRs), while negative-strand ssRNA and dsRNA arboviruses contain few conserved PQSs. The presence of highly conserved PQSs in human arboviruses highlights the potential of non-canonical nucleic acid structures as therapeutic targets in arbovirus infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
R. Aaron Rogers, Madeline R. Meyer, Kayla M. Stewart, Gabriela M. Eyring, Aaron M. Fleming, Cynthia J. Burrows
Summary: The study investigated the pH stability of i-motifs (iM) formed under slightly acidic conditions in DNA-rich sequences, focusing on the effects of different experimental techniques and thermal changes. Results showed that iM analysis methods could impact the pH(T) parameter measured, and hysteresis was observed in both pH(T) and T(m) values.
Article
Chemistry, Multidisciplinary
Aaron M. Fleming, Michael B. Chabot, Ngoc L. B. Nguyen, Cynthia J. Burrows
Summary: The research found that 8-oxoguanine (dOG) is the most reactive in nucleosides, and the native nucleoside dG is higher or similar in reactivity to 5mdC or m(6)A; competition of oxidant in both single- and double-stranded DNA confirmed that dG is favorably oxidized.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Rodrigo Galindo-Murillo, Lauren Winkler, Jingwei Ma, Fatjon Hanelli, Aaron M. Fleming, Cynthia J. Burrows, Thomas E. Cheatham
Summary: This study investigates the specific ligand recognition of abasic sites in G-quadruplex using riboflavin and guanine as examples. The results show that riboflavin can only stabilize abasic site-containing G-quadruplex in the presence of an adjacent OG-modified base.
Article
Biology
Aaron M. Fleming, Cynthia J. Burrows
Summary: The article discusses the oxidation of guanine in DNA caused by ionizing radiation or the Fenton reaction, focusing on the formation of various oxidized lesions including 8-oxo-7,8-dihydroguanine (OG) and 5-carboxamido-5-formamido-2-iminohydantoin (2Ih). It compares the pathways and biological consequences of guanine oxidation induced by hydroxyl radicals with endogenous oxidative stress, emphasizing the potential impact on mutagenesis and epigenetics.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2022)
Article
Chemistry, Organic
Aaron M. Fleming, Songjun Xiao, Michael B. Chabot, Cynthia J. Burrows
Summary: This study found that common fluorescent dyes can act as photosensitizers to oxidize nucleic acids, but with slow rates and low overall yield. This is unlikely to affect most experiments studying nucleic acids, but may have an impact on experiments with long exposures to high-intensity lights, such as sequencing-by-synthesis experiments using fluorescence as the readout.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Michael B. Chabot, Aaron M. Fleming, Cynthia J. Burrows
Summary: Ozonolysis of guanosine leads to the formation of 2Ih nucleoside and trace amounts of Sp. We propose an unconventional ozone mechanism based on literature precedent, which involves the incorporation of one oxygen atom from O3 to form 2Ih and the release of singlet oxygen that is responsible for Sp formation. Experimental evidence using the stabilizing solvent D2O and isotope labeling supports this mechanism and reveals the challenges of working with 2Ih and the context effects on the half-life of the 2Ih glycosidic bond.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Letter
Biology
Cynthia Burrows, Aaron Fleming
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Chemistry, Organic
Michael B. Chabot, Aaron M. Fleming, Cynthia J. Burrows
Summary: Exposure of DNA to oxidants results in modification of the guanine heterocycle, forming the mutagenic 2Ih lesion. Previously believed to exist in a single structure, we have discovered that under biological conditions, 2Ih can reversibly close to an intermediate and open into a newly discovered regioisomer.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Aaron M. Fleming, Songjun Xiao, Cynthia J. Burrows
Summary: The differential reactions of pseudouridine (Psi) and 5-methylcytidine (m(5)C) with NaHSO3 at pH 5 were used to locate their positions in RNA. The study found that NaHSO3 was unique in achieving quantitative yields compared to other reagents. The reaction selectivity of pseudouridine with NaHSO3 was supported by the reaction rate constants at pH 7. Additionally, the Psi derivative N1-methylpseudouridine in mRNA vaccines formed ribose adducts through a similar reaction with bisulfite.
Article
Biochemistry & Molecular Biology
Shereen A. Howpay Manage, Aaron M. Fleming, Hsiao-Nung Chen, Cynthia J. Burrows
Summary: This study provides a quantitative survey of cysteine oxidation to sulfenic acid in APE1 and demonstrates how this modification affects APE1's function towards the NEIL3 gene promoter G4. The research suggests that cysteine oxidation to sulfenic acid enhances APE1's affinity for G4 during oxidative stress, but attenuates its endonuclease activity.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Analytical
Aaron M. Fleming, Renee Tran, Carla A. Omaga, Shereen A. Howpay Manage, Cynthia J. Burrows, John C. Conboy
Summary: This study used SHG to measure the binding interaction between the DNA repair enzyme APE1 and the VEGF promoter G4 folds with AP sites, demonstrating that the interaction is ordered and specific. This resolves the question of how APE1 engages G4 folds with gene regulatory features.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Aaron M. Fleming, Cynthia J. Burrows
Summary: Direct RNA sequencing using a commercial nanopore platform was utilized to sequence RNA molecules with uridine (U), pseudouridine (psi) or N1-methylpseudouridine (m(1)psi) in various contexts. The base calling data for psi and m(1)psi differed from U, allowing their detection. The study examined the selection of UTP, psi TP, or m(1)psi TP by T7 RNA polymerase in different adjacent sequence contexts, finding a significant dependency on sequence context.
NUCLEIC ACIDS RESEARCH
(2023)
Editorial Material
Cell Biology
Aaron M. Fleming, Cynthia J. Burrows
Summary: In the study of DNA modifications, the disciplines of epigenetics and of DNA damage and repair have traditionally been separate. However, it is now recognized that epigenetic modifications require DNA repair pathways for erasure and recent discoveries have shown that oxidative DNA damage can affect gene expression, blurring the lines between these two areas.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Cynthia J. Burrows, Shereen A. Howpay Manage, Aaron M. Fleming, Hsiao-Nung Chen
Summary: This study quantitatively investigated cysteine oxidation to sulfenic acid in APE1 and how this modified form affects APE1's binding to the NEIL3 gene promoter G4; the results suggest that cysteine oxidation can enhance G4 binding but reduce endonuclease activity in APE1, potentially triggering a switch from base excision repair to transcriptional modulation.
ACS CHEMICAL BIOLOGY
(2022)
Meeting Abstract
Environmental Sciences
Jackson I. Gargaro, Cynthia Burrows, Aaron Fleming
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)