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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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Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845
The DNA-damage response in human biology and disease
Jackson, S. P., & Bartek, J. (2009) · Nature · doi:10.1038/nature08467 · Cited by 6,092
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
Johnson, D. S., Mortazavi, A., Myers, R. M., & Wold, B. (2007) · Science · doi:10.1126/science.1141319 · Cited by 2,927
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
Highly prevalent putative quadruplex sequence motifs in human DNA
Todd, A. K. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki553 · Cited by 1,002
Patel, D. J., Phan, A. T., & Kuryavyi, V. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm711 · Cited by 892
Design of Sequence-Specific DNA-Binding Molecules
Dervan, P. B. (1986) · Science · doi:10.1126/science.2421408 · Cited by 838
Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound
Sun, D., Thompson, B., Cathers, B. E., Salazar, M., Kerwin, S. M., Trent, J. O., Jenkins, T. C., Neidle, S., & Hurley, L. H. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm970199z · Cited by 794
ATM-Dependent Chromatin Changes Silence Transcription In cis to DNA Double-Strand Breaks
Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M., & Greenberg, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.04.038 · Cited by 737
Src kinases as therapeutic targets for cancer
Kim, L. C., Song, L., & Haura, E. B. (2009) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.129 · Cited by 700
Targeting RNA with Small Molecules
Thomas, J. R., & Hergenrother, P. J. (2008) · Chemical Reviews · doi:10.1021/cr0681546 · Cited by 657
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining
Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., & Jackson, S. P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1899 · Cited by 629
Self-citationMartin, G. S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35073094 · Cited by 615
Anticancer Activity of CX-3543: A Direct Inhibitor of rRNA Biogenesis
Drygin, D., Siddiqui-Jain, A., O’Brien, S., Schwaebe, M. K., Lin, A. H., Bliesath, J., Ho, C., Proffitt, C., Trent, K., Whitten, J. P., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1304 · Cited by 612
Paeschke, K., Capra, J. A., & Zakian, V. A. (2011) · Cell · doi:10.1016/j.cell.2011.04.015 · Cited by 566 · cited 1×
“Genome-wide analyses have revealed a correlation of Pif1 binding to genomic sequences containing PQSs and to highly transcribed genes, suggesting that Pif1 may also regulate transcriptio”
The Bloom's Syndrome Helicase Unwinds G4 DNA
Sun, H., Karow, J., Hickson, I. D., & Maizels, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.42.27587 · Cited by 554
Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo
Paeschke, K., Simonsson, T., Postberg, J., Rhodes, D., & Lipps, H. J. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb982 · Cited by 531
Rodriguez, R., Müller, S., Yeoman, J. A., Trentesaux, C., Riou, J.-F., & Balasubramanian, S. (2008) · Journal of the American Chemical Society · doi:10.1021/ja805615w · Cited by 517
Self-citationRegulation of gene expression by small molecules
Gottesfeld, J. M., Neely, L., Trauger, J. W., Baird, E. E., & Dervan, P. B. (1997) · Nature · doi:10.1038/387202a0 · Cited by 471
Law, M. J., Lower, K. M., Voon, H. P. J., Hughes, J. R., Garrick, D., Viprakasit, V., Mitson, M., Gobbi, M. D., Marra, M. A., Morris, A. P., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.023 · Cited by 461
Chemical genetics: ligand-based discovery of gene function
Stockwell, B. R. (2000) · Nature Reviews Genetics · doi:10.1038/35038557 · Cited by 418
Leahy, J. J. J., Golding, B. T., Griffin, R. J., Hardcastle, I. R., Richardson, C. J., Rigoreau, L. J. M., & Smith, G. C. M. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.09.060 · Cited by 417
Zabludoff, S., Deng, C., Grondine, M. R., Sheehy, A. M., Ashwell, S., Caleb, B. L., Green, S. A., Haye, H. R., Horn, C. L., Janetka, J. W., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0492 · Cited by 411
Fry, M., & Loeb, L. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.18.12797 · Cited by 371
Ribeyre, C., Lopes, J., Boulé, J., Piazza, A., Guédin, A., Zakian, V., Mergny, J., & Nicolas, A. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000475 · Cited by 367
Takebayashi, Y., Pourquier, P., Zimonjic, D. B., Nakayama, K., Emmert, S., Ueda, T., Urasaki, Y., Kanzaki, A., Akiyama, S., Popescu, N. C., et al. (2001) · Nature Medicine · doi:10.1038/91008 · Cited by 357
An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria gonorrhoeae
Cahoon, L. A., & Seifert, H. S. (2009) · Science · doi:10.1126/science.1175653 · Cited by 310
Epigenetic Instability due to Defective Replication of Structured DNA
Sarkies, P., Reams, C., Simpson, L. J., & Sale, J. E. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.11.009 · Cited by 302
Brooks, T. A., & Hurley, L. H. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2733 · Cited by 299
Eddy, J., & Maizels, N. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkm1138 · Cited by 289
Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA
Cheung, I. K., Schertzer, M. J., Rose, A. M., & Lansdorp, P. M. (2002) · Nature Genetics · doi:10.1038/ng928 · Cited by 270
FANCJ Is a Structure-specific DNA Helicase Associated with the Maintenance of Genomic G/C Tracts
London, T. B. C., Barber, L. J., Mosedale, G., Kelly, G. P., Balasubramanian, S., Hickson, I. D., Boulton, S. J., & Hiom, K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m808152200 · Cited by 252
Self-citationFluorescence Resonance Energy Transfer as a Probe for G-Quartet Formation by a Telomeric Repeat
Mergny, J., & Maurizot, J. (2001) · ChemBioChem · doi:10.1002/1439-7633(20010202)2:2 · Cited by 245
Koirala, D., Dhakal, S., Ashbridge, B., Sannohe, Y., Rodriguez, R., Sugiyama, H., Balasubramanian, S., & Mao, H. (2011) · Nature Chemistry · doi:10.1038/nchem.1126 · Cited by 225
Self-citationGómez, D., Wenner, T., Brassart, B., Douarre, C., O’Donohue, M.-F., El‐Khoury, V., Shin‐ya, K., Morjani, H., Trentesaux, C., & Riou, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605828200 · Cited by 216
Small-molecule-mediated G-quadruplex isolation from human cells
Müller, S., Kumari, S., Rodriguez, R., & Balasubramanian, S. (2010) · Nature Chemistry · doi:10.1038/nchem.842 · Cited by 214
Self-citationPichot, C. S., Hartig, S. M., Xia, L., Arvanitis, C., Monisvais, D., Lee, F. Y., Frost, J. A., & Corey, S. J. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605101 · Cited by 179
CancerGenes: a gene selection resource for cancer genome projects
Higgins, M. E., Claremont, M., Major, J. E., Sander, C., & Lash, A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl811 · Cited by 179
Human Pif1 helicase is a G-quadruplex DNA-binding protein with G-quadruplex DNA-unwinding activity
Sanders, C. M. (2010) · Biochemical Journal · doi:10.1042/bj20100612 · Cited by 156
PARP1 is activated at telomeres upon G4 stabilization: possible target for telomere-based therapy
Salvati, E., Scarsella, M., Porru, M., Rizzo, A., Iachettini, S., Tentori, L., Graziani, G., D’Incalci, M., Stevens, M. F. G., Orlandi, A., et al. (2010) · Oncogene · doi:10.1038/onc.2010.344 · Cited by 123
Deciphering the chromatin landscape induced around DNA double strand breaks
Massip, L., Caron, P., Iacovoni, J. S., Trouche, D., & Legube, G. (2010) · Cell Cycle · doi:10.4161/cc.9.15.12412 · Cited by 68
Nakamoto, T., Miyazaki, Y., Itoi, M., Ono, Y., Kojima, N., & Sorai, M. (2001) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20011217)40:24 · Cited by 53
G-quadruplexes: selective DNA targeting for cancer therapeutics?
Miller, K. M., & Rodriguez, R. (2011) · Expert Review of Clinical Pharmacology · doi:10.1586/ecp.11.4 · Cited by 36
Self-citationRostovtsev, V. V., Green, L. G., Fokin, V. V., & Sharpless, K. B. (2002) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20020715)41:14
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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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