ArticleThe EMBO journal2017
Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Recurrent DNA break clusters drive replication-stress-induced copy number variants and genome diversification.Nature communications · 2026Article
- Emerging roles of RNA:DNA hybrid regulation by mammalian ribonuclease H2 in replication stress and cancer.Journal of cell science · 2025Review
- Genome-wide ribonucleotide detection in Archaea.Nucleic acids research · 2025Article
- Application of Biological Modifiers to a Multiplexed, Human Cell-Based DNA Damage Assay Provides Mechanistic Information on Genotoxicity and Molecular Targets.Environmental and molecular mutagenesis · 2025Article
- Endogenous base damage as a driver of genomic instability in homologous recombination-deficient cancers.DNA repair · 2024Review
- RNase H2 degrades toxic RNA:DNA hybrids behind stalled forks to promote replication restart.The EMBO journal · 2023Article
- Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase.Nature communications · 2023Article
- Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination.eLife · 2022Article
- Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.Cell reports · 2022Article
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Article
- cDNA-detector: detection and removal of cDNA contamination in DNA sequencing libraries.BMC bioinformatics · 2021Article
- Structural basis for proficient oxidized ribonucleotide insertion in double strand break repair.Nature communications · 2021Article
- High Temperature Drives Topoisomerase Mediated Chromosomal Break Repair Pathway Choice.Cancers · 2021Article
- Mechanisms of damage tolerance and repair during DNA replication.Nucleic acids research · 2021Review
- Ribonucleotide incorporation into DNA during DNA replication and its consequences.Critical reviews in biochemistry and molecular biology · 2021Review
- RNases H1 and H2: guardians of the stability of the nuclear genome when supply of dNTPs is limiting for DNA synthesis.Current genetics · 2020Review
- RNA: a double-edged sword in genome maintenance.Nature reviews. Genetics · 2020Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ribonuclease activity of topoisomerase I (Top1) causes DNA nicks bearing 2',3'-cyclic phosphates at ribonucleotide sites. Here, we provide genetic and biochemical evidence that DNA double-strand breaks (DSBs) can be directly generated by Top1 at sites of genomic ribonucleotides. We show that RNase H2-deficient yeast cells displayed elevated frequency of Rad52 foci, inactivation of RNase H2 and RAD52 led to synthetic lethality, and combined loss of RNase H2 and RAD51 induced slow growth and replication stress. Importantly, these phenotypes were rescued upon additional deletion of TOP1, implicating homologous recombination for the repair of Top1-induced damage at ribonuclelotide sites. We demonstrate biochemically that irreversible DSBs are generated by subsequent Top1 cleavage on the opposite strand from the Top1-induced DNA nicks at ribonucleotide sites. Analysis of Top1-linked DNA from pull-down experiments revealed that Top1 is covalently linked to the end of DNA in RNase H2-deficient yeast cells, supporting this model. Taken together, these results define Top1 as a source of DSBs and genome instability when ribonucleotides incorporated by the replicative polymerases are not removed by RNase H2.
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Registered trials
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.