ArticleThe Journal of biological chemistry2015
Topoisomerase I alone is sufficient to produce short DNA deletions and can also reverse nicks at ribonucleotide sites.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 60 citations in OpenAlex.
- DNA damage induces long range changes to duplex structure-a non-protein start to damage detection?Nucleic acids research · 2026Article
- PARP1 regulates the genomic ribonucleotide processing activity of TOP1 to prevent the formation of toxic TOP1-DNA adducts and the associated mutations.bioRxiv : the preprint server for biology · 2026Article
- Brain somatic mutations in Alzheimer's disease: linking genetic mosaicism to neurodegeneration.Molecular neurodegeneration · 2025Review
- Mutations and Recombination at G4 DNA-Forming Sequences Exacerbated by CPT-Resistant Mutant Topoisomerase 1 Is Dependent on SUMOylation.International journal of molecular sciences · 2025Article
- 3,5-Disubstituted pyrazoline as a promising core for anticancer agents: mechanisms of action and therapeutic potentials.Future medicinal chemistry · 2025Review
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- Deletions initiated by the vaccinia virus TopIB protein in yeast.DNA repair · 2024Article
- Transcription as source of genetic heterogeneity in budding yeast.Yeast (Chichester, England) · 2024Review
- Increased binding of anti-dsDNA antibodies to short oligonucleotides modified with topoisomerase I reveals a potential new enzyme function independent from DNA relaxation.BMC research notes · 2023Article
- Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.DNA repair · 2023Article
- Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.Cell reports · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Article
- 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
- Trapped topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.DNA repair · 2020Review
- Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ribonucleotide monophosphates (rNMPs) are among the most frequent form of DNA aberration, as high ratios of ribonucleotide triphosphate:deoxyribonucleotide triphosphate pools result in approximately two misincorporated rNMPs/kb of DNA. The main pathway for the removal of rNMPs is by RNase H2. However, in a RNase H2 knock-out yeast strain, a topoisomerase I (Top1)-dependent mutator effect develops with accumulation of short deletions within tandem repeats. Proposed models for these deletions implicated processing of Top1-generated nicks at rNMP sites and/or sequential Top1 binding, but experimental support has been lacking thus far. Here, we investigated the biochemical mechanism of the Top1-induced short deletions at the rNMP sites by generating nicked DNA substrates bearing 2',3'-cyclic phosphates at the nick sites, mimicking the Top1-induced nicks. We demonstrate that a second Top1 cleavage complex adjacent to the nick and subsequent faulty Top1 religation led to the short deletions. Moreover, when acting on the nicked DNA substrates containing 2',3'-cyclic phosphates, Top1 generated not only the short deletion, but also a full-length religated DNA product. A catalytically inactive Top1 mutant (Top1-Y723F) also induced the full-length products, indicating that Top1 binding independent of its enzymatic activity promotes the sealing of DNA backbones via nucleophilic attacks by the 5'-hydroxyl on the 2',3'-cyclic phosphate. The resealed DNA would allow renewed attempt for repair by the error-free RNase H2-dependent pathway in vivo. Our results provide direct evidence for the generation of short deletions by sequential Top1 cleavage events and for the promotion of nick religation at rNMP sites by Top1.
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