ArticleScience advances2024
Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- TOP1α-mediated stabilization of CYP82C4 G-quadruplex DNA represses lateral root primordium initiation in Arabidopsis.Nature plants · 2026Article
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- R‑loops in hepatocellular carcinoma: Bridging genomic instability and therapeutic opportunity (Review).Molecular medicine reports · 2026Review
- RNA polymerase II is a polar roadblock to a progressing DNA fork.Nature communications · 2025Article
- Protein-mediated stabilization and nicking of the nontemplate DNA strand dramatically affect R-loop formation in vitro.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The paradox of R-loops: guardians of the genome or drivers of disease?Genome research · 2025Review
- Topoisomerase I Inhibition in ETV4-overexpressed Non-Small Cell Lung Cancer Promotes Replication and Transcription Mediated R-Loop Accumulation and DNA Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cancer cells' chamber of secrets: the link between micronuclei, chromothripsis and malignancy.Open biology · 2025Review
- Clues to transcription/replication collision-induced DNA damage: it was RNAP, in the chromosome, with the fork.FEBS letters · 2025Review
- Immunomodulatory effects of trastuzumab deruxtecan through the cGAS-STING pathway in gastric cancer cells.Cell communication and signaling : CCS · 2024Article
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
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Authors and funding
9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, topoisomerase I forms a transient intermediate, topoisomerase I-DNA cleavage complex (Top1cc) to allow strand rotation and duplex relaxation, which can lead to elevated levels of DNA-RNA hybrids and micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data of Top1cc-triggered hybrids and DNA double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid levels with different mechanisms. DSBs are at highly transcribed genes in early replicating initiation zones and overlap with hybrids downstream of accumulated RNA polymerase II (RNAPII) at gene 5'-ends. A transcription factor IIS mutant impairing transcription elongation further increased RNAPII accumulation likely due to backtracking. Moreover, Top1ccs can trigger micronuclei when occurring during late G
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