ArticleeLife2021
Transcription-associated topoisomerase 2α (TOP2A) activity is a major effector of cytotoxicity induced by G-quadruplex ligands.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 90 citations in OpenAlex.
- A complex mutational signature generated by cytarabine resistance.NAR cancer · 2026Article
- RAD54L coordinates the nucleolar DNA damage response to maintain rDNA stability.The EMBO journal · 2026Article
- The UVA-induced single-base mutational signature of CX-5461 in human cells.Nucleic acids research · 2026Article
- G-quadruplex structures as regulators of cellular processes and drivers of genome instability in cancer.Critical reviews in biochemistry and molecular biology · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- The SMARCA4 subunit of the SWI/SNF complex prevents genome instability at G quadruplexes.Genome biology · 2026Article
- DNA topological regulation by topoisomerase IIβ-DNA-PK interaction is important for controlled hypoxia-inducible gene expression.bioRxiv : the preprint server for biology · 2026Article
- DNA damaging properties of G-quadruplex ligand QN-302 are potentiated by the DNA repair inhibitor Olaparib and mitigated by the molecular helicase PhpC.Genome biology · 2026Article
- CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes.G3 (Bethesda, Md.) · 2026Article
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- Photoactivatable, Biomimetic Ligand photoMultiTASQ Traps DNA/RNA G‑Quadruplexes and Their Protein Binding Partners.ACS bio & med chem Au · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- NPM1 mislocalization mediated by RNA Pol I inhibition alters chromatin landscape.bioRxiv : the preprint server for biology · 2025Article
- Reply to: The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells.medRxiv : the preprint server for health sciences · 2025Article
- Hypertranscription of rDNA Responsible for Nucleolar Remodelling is a Doorman for Acquiring Pluripotency.Cell proliferation · 2025Article
- ATRX cooperates with TOP2B for replication fork stability and DNA damage response through G-quadruplex regulation.Nucleic acids research · 2025Article
- ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin.Cell reports · 2025Article
- G-quadruplex stabilization induces DNA breaks in pericentromeric repetitive DNA sequences in B lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pharmacomodulation of G-quadruplexes in long non-coding RNAs dysregulated in colorectal cancer.BMC biology · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G-quadruplexes (G4) are non-canonical DNA structures found in the genome of most species including human. Small molecules stabilizing these structures, called G4 ligands, have been identified and, for some of them, shown to induce cytotoxic DNA double-strand breaks. Through the use of an unbiased genetic approach, we identify here topoisomerase 2α (TOP2A) as a major effector of cytotoxicity induced by two clastogenic G4 ligands, pyridostatin and CX-5461, the latter molecule currently undergoing phase I/II clinical trials in oncology. We show that both TOP2 activity and transcription account for DNA break production following G4 ligand treatments. In contrast, clastogenic activity of these G4 ligands is countered by topoisomerase 1 (TOP1), which limits co-transcriptional G4 formation, and by factors promoting transcriptional elongation. Altogether our results support that clastogenic G4 ligands act as DNA structure-driven TOP2 poisons at transcribed regions bearing G4 structures.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.