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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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Cryo-EM structures of G4-stalled CMG reveal inchworm mechanism of DNA translocationPreprint
Batra, S., Allwein, B., Kumar, C., Devbhandari, S., Brüning, J.-G., Bahng, S., Lee, C., Marians, K. J., Hite, R. K., & Remus, D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.02.616340
Reusable Microfluidic Chambers for Single-Molecule Microscopy
Alfehaid, J., Kodikara, S. G., Alhajri, T., Kabir, M. L., & Balci, H. (2024) · bioRxiv · doi:10.1021/acsami.4c15180
“We used a G-quadruplex (GQ) secondary structure and Replication Protein A (RPA) as the model systems in these studies.”
Dutta, N., Deb, I., Sarzynska, J., & Lahiri, A. (2024) · bioRxiv · doi:10.1101/2024.09.20.614213
“While the structural, thermodynamic, and functional aspects of DNA G-quadruplexes have been widely studied in the past decades [2–5], RNA G-quadruplexes have also emerged as the motif of interest in several theoretical and experimental studies in recent years [6].”
BackgroundEntangled World of DNA Quadruplex Folds
Sundaresan, S., Uttamrao, P., Kovuri, P., & Rathinavelan, T. (2024) · ACS Omega · doi:10.1021/acsomega.4c04579
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“These structures are found in the telomeres of chromosomes, as well as in other regions of the genome, and they play important roles in regulating gene expression and maintaining genomic stability [11 ‒ 13].”
Z jedrsko magnetno resonanco v strukturno raznolikost DNK
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Protein G-quadruplex interactions and their effects on phase transitions and protein aggregation
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“They can stack over one another through π - π integration to form compact and ordered structures (20).”
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“Runs of G have been shown to form G-quadruplex structures that are highly enriched at promoters [79] where they may mediate a variety of functions including epigenetic regulation.”
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WRNIP1 PREVENTS G4/R-LOOP-ASSOCIATED GENOMIC INSTABILITYPreprint
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“[49] In ad- 170 dition, G-quadruplex stabilization can displace shelterin proteins (TRF2 and POT1) and 171 induce a rapid DNA damage response triggering cell death.”
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Folding and Persistence Time of Intramolecular G-Quadruplexes Transiently Embedded in a DNA duplex
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DeepG4 : A deep learning approach to predict active G-quadruplexes from DNAPreprint
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“87] [0-32] [0-100] [0-318] 159 751 000 bp Chr1”
Background
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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