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The Structure and Function of DNA G-Quadruplexes
Open accessAbstract
Guanine-rich DNA sequences can fold into four-stranded, noncanonical secondary structures called G-quadruplexes (G4s). G4s were initially considered a structural curiosity, but recent evidence suggests their involvement in key genome functions such as transcription, replication, genome stability, and epigenetic regulation, together with numerous connections to cancer biology. Collectively, these advances have stimulated research probing G4 mechanisms and consequent opportunities for therapeutic intervention. Here, we provide a perspective on the structure and function of G4s with an emphasis on key molecules and methodological advances that enable the study of G4 structures in human cells. We also critically examine recent mechanistic insights into G4 biology and protein interaction partners and highlight opportunities for drug discovery.
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“Lastly, more serious DNA damages, such as double-strand breaks associated with non-B DNA structures like G4s, and the subsequent DNA repair can be mutagenic (7,27).”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [7]
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DNA folds threaten genetic stability and can be leveraged for chemotherapy
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“G4 can be formed of DNA [5] or RNA [6].”
BackgroundMetal-Based G-Quadruplex Binders for Cancer Theranostics
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“reported a series of Re(I)–tricarbonyl complexes containing the facially coordinated [1,4,7]-triazacyclononane (TACN) ligand, which was covalently linked to a porphyrin scaffold that can act as a photosensitizer (PS) and also as a π-stacking core to achieve G4 selectivity [151].”
BackgroundWater spines and networks in G-quadruplex structures
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Phthalocyanines for G-quadruplex aptamers binding.
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G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation
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G-quadruplexes in cancer-related gene promoters: from identification to therapeutic targeting
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“Among these non-canonical DNA conformations, G4s are by far the most extensively investigated structures due to their role in peculiar regions of the genome [6].”
BackgroundInfluentialCurrent Developments of N-Heterocyclic Carbene Au(I)/Au(III) Complexes toward Cancer Treatment
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Global mapping of RNA G-quadruplexes (G4-RNAs) using G4RP-seq
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“A complete G4 is assembled from at least two G-tetrads stacked one above another, and is stabilised by monovalent cations located in the ion channel (5,9).”
Cellular Visualization of G-Quadruplex RNA via Fluorescence- Lifetime Imaging Microscopy
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Predicting Genetic Disorder and Types of Disorder Using Chain Classifier Approach
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Zuo1 supports G4 structure formation and directs repair toward nucleotide excision repair
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Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy
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Rotaxanes as cages to control DNA binding, cytotoxicity and cellular uptake of a small molecule.
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Overview of the materials design and sensing strategies of nanopore devices
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PENGUINN: Precise Exploration of Nuclear G-Quadruplexes Using Interpretable Neural Networks
Klimentová, E., Poláček, J., Šimeček, P., & Alexiou, P. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.568546 · Cited by 42
“G4s are known to play important roles in several biological processes, such as DNA replication, damage response, RNA transcription and processing, transcriptional and translational regulation and others (Spiegel et al., 2020).”
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DNA Sequence and Length Dictate the Assembly of Nucleic Acid Block Copolymers.
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Structural Unfolding of G-Quadruplexes: From Small Molecules to Antisense Strategies
Fracchioni, G., Vailati, S., Grazioli, M., & Pirota, V. (2024) · Molecules · doi:10.3390/molecules29153488 · Cited by 30
“…strands have the same direction and the fourth is oriented oppositely ( Moreover, G4 structures can be intramolecular, originating from a single nucleotide sequence, or bimolecular or tetramolecular, involving the intermolecular interaction of two or four nucleotide filaments, respectively [8].”
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Telomere-specific regulation of TERRA and its impact on telomere stability
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Metadata
- Authors
- Spiegel, J., Adhikari, S., & Balasubramanian, S.
- Affiliations
- Cancer Research UK (GB)
- University of Cambridge (GB)
- Corresponding author
- Balasubramanian, Shankar
- Venue
- Trends in Chemistry
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 2
- Issue
- 2
- Pages
- 123-136
- ISSN
- 2589-5974 (ISSN-L)
- PMC
- PMC7472594
- OpenAlex
- W2966334511
- Cited by
- 920
- References
- 121
- Citations by year
- 2026: 111 · 2025: 157 · 2024: 158 · 2023: 144 · 2022: 151 · 2021: 122 · 2020: 74
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in Chemistry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Wellcome Trust
- Cancer Research UK
- Horizon 2020 Framework Programme
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Keywords
- G-quadruplex, guanine-rich DNA, genome stability, transcription, DNA replication, epigenetic regulation, cancer, G-quadruplex-binding proteins
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