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Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds
Open accessAbstract
G-quadruplex (G4)-forming genomic sequences, including telomeres, represent natural replication fork barriers. Stalled replication forks can be stabilized and restarted by homologous recombination (HR), which also repairs DNA double-strand breaks (DSBs) arising at collapsed forks. We have previously shown that HR facilitates telomere replication. Here, we demonstrate that the replication efficiency of guanine-rich (G-rich) telomeric repeats is decreased significantly in cells lacking HR. Treatment with the G4-stabilizing compound pyridostatin (PDS) increases telomere fragility in BRCA2-deficient cells, suggesting that G4 formation drives telomere instability. Remarkably, PDS reduces proliferation of HR-defective cells by inducing DSB accumulation, checkpoint activation, and deregulated G2/M progression and by enhancing the replication defect intrinsic to HR deficiency. PDS toxicity extends to HR-defective cells that have acquired olaparib resistance through loss of 53BP1 or REV7. Altogether, these results highlight the therapeutic potential of G4-stabilizing drugs to selectively eliminate HR-compromised cells and tumors, including those resistant to PARP inhibition.
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“This effect seems to be aggravated in cells with an impaired DNA repair machinery and deficiencies in homologous recombination. (72).”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [72]
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Sorted by citations
Items 101–200 of 231
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UV-induced G4 DNA structures recruit ZRF1 which prevents UV-induced senescence
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InfluentialVariation in G-quadruplex sequence and topology differentially impacts human DNA polymerase fidelity
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“Recent genome-wide studies have demonstrated the prevalence of G4 sequences and structures in the promoters of highly expressed cancer genes and near chromosomal breakpoints for these genes, suggesting their physiological importance in the regulation of cancer gene expression,(10,13,44) as well as their utility as tar…”
BackgroundG-quadruplex-mediated genomic instability drives SNVs in cancer
Richl, T., Kuper, J., & Kisker, C. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae098 · Cited by 20
“( 72 ).”
Mock, P. Y., Chua, E. W., Yen, K. P., Stevens, A. J., & Lam, K. W. (2023) · Future Medicinal Chemistry · doi:10.4155/fmc-2023-0202 · Cited by 25
Lee, J., Sung, K., Joo, S. Y., Jeong, J.-H., Kim, S. K., & Lee, H. (2022) · Nature Communications · doi:10.1038/s41467-022-31156-z · Cited by 23
Therapeutic Use of G4-Ligands in Cancer: State-of-the-Art and Future Perspectives
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“…the preclinical results showing the capability of CX-5461 to trigger synthetic lethality in BRCA-deficient tumors resistant to PARP inhibitors [24,53], this G4 ligand is currently entered into phase Ib clinical trials (NCT04890613) as a drug for the treatment of cancer patients with germline…”
BackgroundSelf-citationHan, Y.-C., Buric, A., Chintareddy, V., DeMoss, M., Chen, L., Dickerhoff, J., Dios, R. K. D., Chand, P., Riggs, R., Yang, D.-Z., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c02303 · Cited by 19
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Chemical targeting of G-quadruplexes in telomeres and beyond for molecular cancer therapeutics
Seimiya, H., Nagasawa, K., & Shin‐ya, K. (2021) · The Journal of Antibiotics · doi:10.1038/s41429-021-00454-x · Cited by 21
Fundamentals of G-quadruplex biology
Johnson, F. B. (2020) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2020.06.004 · Cited by 29
“RAD51 mutant cells are hypersensitive to PDS, which correlates with elevated levels of telomere fragility, and holds true even for those that are resistant to olpaparib.(207) Similarly, cells deficient in BRCA1, BRCA2, or the non-homologous end joining factors LIG4 and DNA-PK, are hypersensi-”
Distinct functions of human RecQ helicases during DNA replication
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BLM and BRCA1-BARD1 coordinate complementary mechanisms of joint DNA molecule resolution
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“Interestingly, administration of the G4 stabilizing small molecule compounds slows down the replication and stops the replication forks [24].”
BackgroundLim, Y., Ensbey, K., Offenhäuser, C., D'Souza, R. C. J., Cullen, J. K., Stringer, B., Quek, H., Bruce, Z. C., Kijas, A., Cianfanelli, V., et al. (2019) · Neuro-Oncology · doi:10.1093/neuonc/noz159 · Cited by 18
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“PDS treatment suppressed cellular viability in BRCA2-depleted HeLa LT TERC KO cells, consistent with a previous report ( 47 ) (Figure 6 C).”
BackgroundResultDNA repair protein RAD52 is required for protecting G-quadruplexes in mammalian cells
Liu, S., Wang, Z., Shah, S. B., Chang, C., Ai, M., Nguyen, T., Xiang, R., & Wu, X. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102770 · Cited by 14
“G4-stabilizing drugs have been used for cancer treatment (51, 52), and they exhibit more toxic effects in BRCA1/2deficient and ATRX-deficient cancer cells (33, 53).”
Alternative paths to telomere elongation
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Ubiquitination and SUMOylation in Telomere Maintenance and Dysfunction
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“Also, when replication at telomeres stalls because of topological barriers that cannot be resolved by helicases, a DDR is activated to restart replication through HR (Badie et al., 2010; Tacconi and Tarsounas, 2015; Zimmer et al., 2016).”
BackgroundG-quadruplex ligands as potent regulators of lysosomes
Ferret, L., Alvarez-Valadez, K., Rivière, J., Müller, A., Bohálová, N., Luo, Y., Guittat, L., Brázda, V., Kroemer, G., Mergny, J., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2170071 · Cited by 17
“It is worth noting that some G4L elicit DNA damage responses and cell killing and have been shown to be particularly effective in cancer cells deficient in DNA repair genes [32,33].”
BackgroundSperti, F. R., Dupouy, B., Mitteaux, J., Pipier, A., Pirrotta, M., Chéron, N., Valverde, I. E., & Monchaud, D. (2022) · JACS Au · doi:10.1021/jacsau.2c00082 · Cited by 19
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Telomere replication—When the going gets tough
Stroik, S., & Hendrickson, E. A. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102875 · Cited by 15
Manipulating Adult Neural Stem and Progenitor Cells with G-Quadruplex Ligands
Goldberg, D. C., Fones, L., Vivinetto, A. L., Caufield, J. T., Ratan, R. R., & Cave, J. W. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00194 · Cited by 17
Cytotoxic and genotoxic effects of Benzo[ghi]perylene on the human bronchial cell line NL-20
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“In consideration of this, our data support a view in which ALT mechanism could be at the basis of a higher sensitivity of BRCA2 cells to some G-quadruplex ligands such as Pyridostatin and CX-5461 [29,38].”
BackgroundSelf-citationA transcription-based mechanism for oncogenic β-catenin-induced lethality in BRCA1/2-deficient cells
Dagg, R. A., Zonderland, G., Lombardi, E. P., Rossetti, G. G., Groelly, F. J., Barroso, S. I., Tacconi, E. M., Wright, B., Lockstone, H. E., Aguilera, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25215-0 · Cited by 14
Self-citationHERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN
Zhu, M., Wu, W., Togashi, Y., Liang, W., Miyoshi, Y., & Ohta, T. (2021) · Scientific Reports · doi:10.1038/s41598-020-79715-y · Cited by 14
Targeting DNA repair pathways: mechanisms and potential applications in cancer therapy
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“, G-quadruplex-binding compounds) (Zimmer et al., 2016).”
BackgroundTWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro
Guyon, L., Pirrotta, M., Duskova, K., Granzhan, A., Teulade‐Fichou, M., & Monchaud, D. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1118 · Cited by 21
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“Recently, it has been shown that HR proteins, such as Rad51 and BRCA1, regulate HR at G4 structures during DNA replication (51).”
BackgroundDNA G-quadruplexes: Structural and functional insights
Jonchhe, S., Lahiri, S., & Rothenberg, E. (2025) · DNA repair · doi:10.1016/j.dnarep.2025.103910 · Cited by 13
Merlino, F., Marzano, S., Zizza, P., D’Aria, F., Grasso, N., Carachino, A., Iachettini, S., Biroccio, A., Fonzo, S. D., Grieco, P., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae471 · Cited by 19
“…with a key role in homologous recombination and DNA repair ( 68 ), it is also possible to assert that these peptides, unlike most known G4 ligands which are mainly effective in BRCA-deficient models ( 1 , 69 , 70 ), promote their activity also in tumour cells able to potentially repair DNA damage.”
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“By-product bis-oxazolepyridine (16) and starting material 18 were also isolated respectively in 7% and 42 % yield.”
BackgroundThe Helicase PIF1 Facilitates Resection over Sequences Prone to Forming G4 Structures
Jimeno, S., Camarillo, R., Mejías-Navarro, F., Fernández-Ávila, M. J., Soria‐Bretones, I., Prados‐Carvajal, R., & Huertas, P. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.047 · Cited by 50
Roles of G4-DNA and G4-RNA in Class Switch Recombination and Additional Regulations in B-Lymphocytes
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“BRCA1 and BRCA2, two tumor suppressor genes that interact with G4 structures [164], participate in homologous recombination and thus allow the repair of DNA DSBs.”
BackgroundThe effect of side chain variations on quinazoline-pyrimidine G-quadruplex DNA ligands.
Bhuma, N., Chand, K., Andréasson, M., Mason, J., Das, R., Patel, A. K., Öhlund, D., & Chorell, E. (2023) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2023.115103 · Cited by 11
“Furthermore, it has been shown that G4 DNA stabilizing compounds are highly effective against tumors with dysfunctional DNA repair mechanisms, including those that have acquired resistance to PARP inhibitors [31].”
Shen, Z., Zheng, R.-L., Yang, H.-M., Xing, S., Jin, X.-X., Yan, H., Zhu, J.-F., Mei, Y.-N., Lin, F., & Zheng, X.-H. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.06.015 · Cited by 11
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“Of note, pyridostatin could overcome resistance to Olaparib in homologous recombination-defective cells [244].”
BackgroundDiscovery of MTR-106 as a highly potent G-quadruplex stabilizer for treating BRCA-deficient cancers
Li, M.-Z., Meng, T., Song, S.-S., Bao, X.-B., Ma, L.-P., Zhang, N., Yu, T., Zhang, Y.-L., Xiong, B., Shen, J.-K., et al. (2021) · Investigational new drugs · doi:10.1007/s10637-021-01096-4 · Cited by 11
G-Quadruplex Nucleic Acids: Methods and Protocols
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“…that stabilize G4 leads to multiple DNA damage [14], micronuclei formation, delayed replication fork progression [15], and telomeric defects [16–18]. treatment of cancer-specific cells and transcriptional alteration [14], the binding of other ligands that stabilize G4 leads to multiple DNA…”
Nuccio, S. P., Cadoni, E., Nikoloudaki, R., Galli, S., Ler, A.-J., Sanchez-Cabanillas, C., Maher, T. E., Fan, E., Guneri, D., Flint, G., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67074-z · Cited by 25
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“While G4 resolution under physiological conditions helps maintain genomic stability, small molecules that stabilize G4s convert these transient structures into persistent replication and transcription barriers, leading to fork stalling, DNA damage, and genome instability [ 10 , 11 ].”
InfluentialHarnessing G-quadruplex ligands for lung cancer treatment: A comprehensive overview
Figueiredo, J., Djavaheri‐Mergny, M., Ferret, L., Mergny, J., & Cruz, C. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103808 · Cited by 9
Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox
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“For example, cells with impaired homologous recombination repair pathways (which includes cells deficient in BRCA1 and BRCA2) display higher levels of genomic instability, cell cycle arrest and apoptosis following stabilization of G4 structures (199).”
BackgroundThe fellowship of the RING: BRCA1, its partner BARD1 and their liaison in DNA repair and cancer
Russi, M., Marson, D., Fermeglia, A., Aulić, S., Fermeglia, M., Laurini, E., & Pricl, S. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108009 · Cited by 14
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Transcriptional regulation of MYC through G-quadruplex structures
Balaratnam, S., & Schneekloth, J. S. (2020) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2020.05.002 · Cited by 12
Lee, M.-G., Hong, H.-J., & Nam, K.-S. (2023) · Pharmaceuticals · doi:10.3390/ph17010024 · Cited by 8
Joint Efforts of Replicative Helicase and SSB Ensure Inherent Replicative Tolerance of G‐Quadruplex
Guo, L., Bao, Y., Zhao, Y., Ren, Z., Bi, L., Zhang, X., Liu, C., Hou, X., Wang, M. D., & Sun, B. (2023) · Advanced Science · doi:10.1002/advs.202307696 · Cited by 10
Datta, A., & Brosh, R. M. (2022) · BioEssays · doi:10.1002/bies.202200057 · Cited by 9
G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency
Kim, S., & Hwang, S. (2022) · Genes · doi:10.3390/genes13030391 · Cited by 8
Challenges in developing small-molecule quadruplex therapeutics
Neidle, S. (2020) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2020.05.005 · Cited by 11
Simoes‐Sousa, S., Amin, N., Lane, K. A., Harrod, A., Pedersen, M., Pardo, M., Rasetti‐Escargueil, C., Kozik, Z., Begg, K., Ribeiro, A., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116277 · Cited by 7
Pirota, V., Iachettini, S., Platella, C., Zizza, P., Fracchioni, G., Vito, S. D., Carachino, A., Battistini, F., Orozco, M., Freccero, M., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf301 · Cited by 10
“8 C), indicating that these compounds—differently from other known G4 stabilizing agents [ 27 ]—exert their activity also in cells able to repair the DNA damage.”
Self-citationAdvances in Glioblastoma Diagnosis: Integrating Genetics, Noninvasive Sampling, and Advanced Imaging
Gough, R., Treffy, R., Krucoff, M. O., & Desai, R. R. (2025) · Cancers · doi:10.3390/cancers17010124 · Cited by 12
“However, further study of the prognostic implications of ATRX is necessary, and investigations of ATRX and related pathways as a target are ongoing, given its implication in increasing sensitivity to DNA-damaging agents [63,65,69,70].”
Looping forward: exploring R‐loop processing and therapeutic potential
Stratigi, K., Siametis, A., & Garinis, G. A. (2024) · FEBS Letters · doi:10.1002/1873-3468.14947 · Cited by 9
Why to target G‐quadruplexes using peptides: Next‐generation G4‐interacting ligands
Sharma, T., Kundu, N., Kaur, S., Shankaraswamy, J., & Saxena, S. (2023) · Journal of Peptide Science · doi:10.1002/psc.3491 · Cited by 11
Li, J.-H., Ma, T.-Z., Fu, J.-L., Huang, J.-T., Zhang, M.-J., You, P.-D., & Zhou, C.-Q. (2021) · Dyes and Pigments · doi:10.1016/j.dyepig.2021.109304 · Cited by 7
Doria, F., Nadai, M., Costa, G., Sattin, G., Gallati, C. M., Bergamaschi, G., Moraca, F., Alcaro, S., Freccero, M., & Richter, S. N. (2016) · European Journal of Organic Chemistry · doi:10.1002/ejoc.201600757 · Cited by 9
G-quadruplex stabilization via small molecules as a potential anti-cancer strategy
Li, C., Liu, J., & Wang, R. (2026) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-026-00890-3 · Cited by 6
“In addition, other G4 ligands, such as QN-302 and PDS, have shown antitumor activity and enhanced telomere instability in BRCA -defi- cient contexts [158].”
Cooperative interaction of CST and RECQ4 resolves G‐quadruplexes and maintains telomere stability
Li, T., Zhang, M., Li, Y., Han, X., Tang, L., Ma, T., Zhao, X., Zhao, R., Wang, Y., Bai, X., et al. (2023) · EMBO Reports · doi:10.15252/embr.202255494 · Cited by 8
“Previous studies have shown that PDS induces G4 formation and replication fork stalling, leading to the activation of the DNA damage response (McLuckie et al , 2013; Zimmer et al , 2016).”
Si, M. K., Pramanik, S. K., & Ganguly, B. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.12.019 · Cited by 7
G‐Quadruplexes in Gene Regulation and Cellular Function
Wen, Q., Guo, L., Bordbar, F., & Nie, Q. (2025) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.70019 · Cited by 6
“RPA binds to Rad51, BRCA1, and BRCA2, and protects ssDNA created during replication and repair from degradation and pairing with the complementary strand (Chen et al. 2008; Gauthier et al. 2012; Zimmer et al. 2016).”
Waisertreiger, I. S.-R., Ayele, K., Elshaikh, M. H., & Barlow, J. H. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2506939122 · Cited by 6
“PDS was shown to promote telomeric chromosomal instability in some cancer cell lines ( 22 ), however studies evaluating the effect of PDS on overall chromosomal stability are limited.”
InfluentialTMPRSS2 isoform 1 downregulation by G-quadruplex stabilization induces SARS-CoV-2 replication arrest
Magis, A. D., Schult, P., Schönleber, A., Linke, R., Ludwig, K. U., Kümmerer, B. M., & Paeschke, K. (2024) · BMC Biology · doi:10.1186/s12915-023-01805-w · Cited by 4
Wu, G., & Han, H. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9666-7_12 · Cited by 11
Rare genetic diseases associated with G-quadruplex-induced replication stress
Herr, L. M., Mukhopadhyay, S., Anderson, O. M., Couch, T. H., Jones, C. M., Brosh, R. M., & Rossi, M. S. (2026) · Communications Biology · doi:10.1038/s42003-026-09966-4 · Cited by 4
Hile, S. E., Weissensteiner, M. H., Pytko, K. G., Dahl, J. M., Kejnovský, E., Kejnovská, I., Hedglin, M., Georgakopoulos‐Soares, I., Makova, K. D., & Eckert, K. A. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf352 · Cited by 4
“Small molecule G4-stabilizing ligands, such as PDS, have been studied for their therapeutic potential to target cancer cells [ 108 , 109 ].”
Extraordinary collateral mutagenesis induced by CX-5461
Boulton, S. (2023) · Nature Genetics · doi:10.1038/s41588-023-01611-8 · Cited by 4
Camarillo, R., Jimeno, S., & Huertas, P. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.742434 · Cited by 5
Petrov, N., Lee, H.-S., Liskovykh, M., Teulade-Fichou, M., Masumoto, H., Earnshaw, W., Pommier, Y., Larionov, V., & Kouprina, N. (2021) · OncoTarget · doi:10.18632/oncotarget.28020 · Cited by 4
“It is worth noting that we cannot exclude additional mechanisms of action for these G4 ligands, including transcriptional inactivation of genes important for chromosome segregation or induction of chromosomal DSBs as previously was described for other G4 stabilizers [49, 50].”
BackgroundDDIAS shields single-stranded DNA in mitosis and promotes vertebrate brain development
Tsukada, K., Lototska, L., 塚田, 絢., Sarusie, M. V., Gönenç, I. I., Sherlaw‐Sturrock, C., Kanade, M., Palek, M., Oliver, A. W., Jones, S. E., et al. (2026) · Cell · doi:10.1016/j.cell.2026.07.041 · Cited by 5
BRCA2 Haploinsufficiency in Telomere Maintenance
Gunnarsdottir, S. R., Bjarnason, H., Þorvaldsdóttir, B., Paland, F., Steinarsdóttir, M., Eyfjord, J. E., & Böðvarsdóttir, S. K. (2021) · Genes · doi:10.3390/genes13010083 · Cited by 4
“BRCA2 is required for telomere replication of the G-rich strand that has a high propensity to adopt G-quadruplex secondary structures leading to MTS formation in BRCA2 deficient cells [38].”
BackgroundG-quadruplex–R-loop interactions and the mechanism of anticancer G-quadruplex binders
Miglietta, G., Russo, M., & Capranico, G. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1206 · Cited by 3
“The knowledge came from observations in cancer cells deficient for BRCA1/2 genes, critical players of HRR, as G4 binders were shown to be more active in DSB accumulation and persistent checkpoint activation in these cell types (112).”
BackgroundMutagen-induced telomere instability in human cells
Bolzán, A. D. (2021) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2021.503387 · Cited by 5
Granzhan, A., Martins, R. P., Fåhraeus, R., Blondel, M., & Teulade-Fichou, M. (2020) · Annual Reports in Medicinal Chemistry · doi:10.1016/bs.armc.2020.05.001 · Cited by 3
DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosisPreprint
Tsukada, K., Lototska, L., Tsukada, A., Gönenç, I. I., Sherlaw-Sturrock, C. A., Kanade, M., Oliver, A. W., Jones, S. E., Jhujh, S. S., Bannister, J., et al. (2026) · bioRxiv · doi:10.1101/2025.09.09.675193 · Cited by 2
G quadruplex DNA facilitates a pervasive path to homologous recombinationPreprint
Thakur, B. L., Basak, P., Khurana, S., Sharma, S., Lai, Y.-H., Nguyen, T., Ramanarayanan, V., Zhao, X., Batista, P. J., Stracker, T. H., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.05.730358 · Cited by 1
“In contrast, G4 stabilizing drugs were found to be cytotoxic in cells lacking BRCA1, BRCA2 or RAD51 in vitro ( 52 ), likely reflecting dose dependence and/or di\erences between global G4 stabilization and more selective G4 modulation upon DHX36 inactivation ( 22 ).”
Luchian, T., Cimpanu, A., Park, J., Mereuta, L., & Park, Y. (2026) · Small Methods · doi:10.1002/smtd.70691 · Cited by 2
DNA G-quadruplex profiling in skeletal muscle stem cells reveals functional and mechanistic insights
Chen, X., Yang, F., Zhang, S., Guo, X., Zhao, J., Qiao, Y., He, L., Li, Y., Zhou, Q., Ong, M. T., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03753-w · Cited by 6
“To rule out the possibility that PDS treatment inhibits proliferation through its known effects on inducing DNA damage and genome instability [44, 45], we performed the IF staining of γH2AX and found that PDS treatment did not cause significant change of genomic stability in ASCs (Additional file…”
Keahi, D., Sanders, M. A., Paul, M. R., Webster, A., Fang, Y., Wiley, T. F., Shalaby, S., Carroll, T. S., Chandrasekharappa, S. C., Sandoval-Garcia, C., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2503872122 · Cited by 2
“The connection of G4s and BRCA2 may also be important in other settings of BRCA1/2 deficiency, as the stabilization of G4 DNA by PDS leads to cell death in BRCA1/2 - deficient cells ( 52 ) and in patient derived xenografts ( 25 ).”
Metal–stabilized G–quadruplexes: biological insights and sensing applications
Kim, S.-M., Kim, D., & Kim, Y. (2025) · BMB Reports · doi:10.5483/bmbrep.2025-0048 · Cited by 2
The effect of prolonged G-quadruplex stabilization on the functions of human cells
Karatayeva, N., Hegedűs, L., Bhattacharjee, A., Németh, E., Póti, Á., Pongor, L. S., Juhász, G., Szüts, D., & Burkovics, P. (2025) · Scientific Reports · doi:10.1038/s41598-025-04791-x · Cited by 4
“The repair of DSBs could result in genomic instability such as insertions, deletions or chromosome rearrangements.”
Joo, S. Y., Sung, K., & Lee, H. (2024) · BioEssays · doi:10.1002/bies.202300229 · Cited by 3
“[114] BRCA1/2-deficient cells exhibit selective sensitivity towards chemical ligands that stabilize G4 structures, such as PDS [119] or CX-5461.”
Desai, N., Shah, V., & Datta, B. (2021) · Molecules · doi:10.3390/molecules26051400 · Cited by 2
“Interestingly, while TMPyP4 [35], piperine [36], and quarfloxin [37,38] are well-known G4 DNA stabilizers, there are only a few indirect reports on the interaction of olaparib with quadruplex DNA [39].”
Background
Metadata
- Authors
- Zimmer, J., Tacconi, E. M. C., Folio, C., Badie, S., Porru, M., Klare, K., Tumiati, M., Markkanen, E., Halder, S., Ryan, A., Jackson, S. P., Ramadan, K., Kuznetsov, S. G., Biroccio, A., Sale, J. E., & Tarsounas, M.
- Affiliations
- University of Oxford (GB)
- Instituto Nazionale Tumori Regina Elena (IT)
- University of Helsinki (FI)
- University of Cambridge (GB)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Tarsounas, Madalena
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 61
- Issue
- 3
- Pages
- 449-460
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4747901
- OpenAlex
- W2207187217
- Cited by
- 261
- References
- 58
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 32 · 2023: 28 · 2022: 22 · 2021: 37 · 2020: 33 · 2019: 25 · 2018: 16 · 2017: 22 · 2016: 9
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (WT092096, 092096)
- Cancer Research UK (17201, 18796, S_3001, 11224)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (141197)
- Medical Research Council (MC_PC_12001/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- G-quadruplex, BRCA1, BRCA2, homologous recombination deficiency, telomere replication, telomere instability, pyridostatin, DNA damage checkpoint, G2/M transition, olaparib resistance, 53BP1, REV7, PARP inhibitor resistance, replication fork collapse
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Tumor Suppressor p53-Binding Protein 1, Aminoquinolines, Animals, Antineoplastic Agents, Dose-Response Relationship, Drug, Humans, Male, Mice, Nude, Neoplasms, Picolinic Acids, Time Factors, Transfection, Biomarkers, Tumor, Telomere, Drug Resistance, Neoplasm, BRCA1 Protein, Xenograft Model Antitumor Assays, BRCA2 Protein, RNA Interference, Tumor Burden, Intracellular Signaling Peptides and Proteins, Cell Proliferation, DNA Breaks, Double-Stranded, G-Quadruplexes, HEK293 Cells, Molecular Targeted Therapy, G2 Phase Cell Cycle Checkpoints, Mad2 Proteins
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