The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Small-molecule–induced DNA damage identifies alternative DNA structures in human genes
Open accessAbstract
Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. A chromatin immunoprecipitation sequencing analysis of the DNA damage marker γH2AX provided the genome-wide distribution of pyridostatin-induced sites of damage and revealed that pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto-oncogene SRC. We observed that pyridostatin reduced SRC protein abundance and SRC-dependent cellular motility in human breast cancer cells, validating SRC as a target of this drug. Our unbiased approach to define genomic sites of action for a drug establishes a framework for discovering functional DNA-drug interactions.
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“there is strong evidence that deregulated G4-formation is a major driver of genomic instability”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [26]
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“Error-prone polymerases might be engaged at slowed or stalled replication forks to ensure complete G4 replication, as specialized polymerases like eta, kappa, and Rev1 are essential for G4 stability – further increasing the density of localized genomic damages (26,78–80).”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [26]
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Cites
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High-Resolution Profiling of Histone Methylations in the Human Genome
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The DNA-damage response in human biology and disease
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Self-citationThe DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368
Genome-Wide Mapping of in Vivo Protein-DNA Interactions
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Siddiqui-Jain, A., Grand, C. L., Bearss, D. J., & Hurley, L. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182256799 · Cited by 2,274
Prevalence of quadruplexes in the human genome
Huppert, J. L., & Balasubramanian, S. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki609 · Cited by 1,795
Self-citationHickson, I., Zhao, Y., Richardson, C. J., Green, S. J., Martin, N. M. B., Orr, A. I., Reaper, P. M., Jackson, S. P., Curtin, N. J., & Smith, G. C. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2727 · Cited by 1,220
Self-citationYeatman, T. J. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1366 · Cited by 1,113
Cited by
Sorted by citations
Quantitative visualization of DNA G-quadruplex structures in human cells
Biffi, G., Tannahill, D., McCafferty, J., & Balasubramanian, S. (2013) · Nature Chemistry · doi:10.1038/nchem.1548 · Cited by 2,173
Self-citationG-quadruplexes and their regulatory roles in biology
Rhodes, D., & Lipps, H. J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv862 · Cited by 1,537
DNA secondary structures: stability and function of G-quadruplex structures
Bochman, M. L., Paeschke, K., & Zakian, V. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3296 · Cited by 1,485
The regulation and functions of DNA and RNA G-quadruplexes
Varshney, D., Spiegel, J., Zyner, K. G., Tannahill, D., & Balasubramanian, S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0236-x · Cited by 1,292
Self-citationHigh-throughput sequencing of DNA G-quadruplex structures in the human genome
Chambers, V. S., Marsico, G., Boutell, J. M., Antonio, M. D., Smith, G. P., & Balasubramanian, S. (2015) · Nature Biotechnology · doi:10.1038/nbt.3295 · Cited by 1,261
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Metadata
- Authors
- Rodriguez, R., Miller, K. M., Forment, J. V., Bradshaw, C. R., Nikan, M., Britton, S., Oelschlaegel, T., Xhemalce, B., Balasubramanian, S., & Jackson, S. P.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Balasubramanian, Shankar
- Jackson, Stephen P
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2012-02-05
- Volume
- 8
- Issue
- 3
- Pages
- 301-310
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3433707
- OpenAlex
- W2042374693
- Cited by
- 741
- References
- 50
- Citations by year
- 2026: 35 · 2025: 55 · 2024: 66 · 2023: 53 · 2022: 41 · 2021: 60 · 2020: 58 · 2019: 56 · 2018: 52 · 2017: 52 · 2016: 39 · 2015: 54 · 2014: 49 · 2013: 44 · 2012: 27
- FWCI
- 22.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (092096/Z/10/Z, 086861/Z/08/Z, 086861, 092096)
- Cancer Research UK (11961, C6/A11224, 11224, A11224, C9681/A11961)
- Biotechnology and Biological Sciences Research Council (BB/G008337/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- pyridostatin, G-quadruplex, alternative DNA structures, DNA damage, γH2AX, cell cycle arrest, breast cancer, guanine-rich DNA, gene expression regulation, drug-DNA interaction, ChIP-seq
- MeSH terms
- Proto-Oncogene Mas, Aminoquinolines, Antineoplastic Agents, Breast Neoplasms, Cell Cycle, DNA, DNA Damage, Drug Screening Assays, Antitumor, Humans, Molecular Weight, Picolinic Acids, Structure-Activity Relationship, Tumor Cells, Cultured, Cell Proliferation, G-Quadruplexes
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