ArticleThe Journal of biological chemistry2009
Proteasome-dependent processing of topoisomerase I-DNA adducts into DNA double strand breaks at arrested replication forks.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- Prpf4 sequentially regulates the expansion and maturation of erythrocyte through distinct mechanisms.Cell death discovery · 2025Article
- Patulin and Xestoquinol are inhibitors of DNA topoisomerase 1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Mechanisms controlling replication fork stalling and collapse at topoisomerase 1 cleavage complexes.Molecular cell · 2024Article
- Chromodomain mutation in S. pombe Kat5/Mst1 affects centromere dynamics and DNA repair.PloS one · 2024Article
- Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex.Nature communications · 2023Article
- MUS81 cleaves TOP1-derived lesions and other DNA-protein cross-links.BMC biology · 2023Article
- Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation.International journal of molecular sciences · 2023Review
- Short-Term Starvation Weakens the Efficacy of Cell Cycle Specific Chemotherapy Drugs through G1 Arrest.International journal of molecular sciences · 2023Article
- Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer.Communications biology · 2022Article
- CDK7 Inhibition Synergizes with Topoisomerase I Inhibition in Small Cell Lung Cancer Cells by Inducing Ubiquitin-Mediated Proteolysis of RNA Polymerase II.Molecular cancer therapeutics · 2022Article
- SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases.Frontiers in molecular biosciences · 2022Review
- Cellular functions of the protein kinase ATM and their relevance to human disease.Nature reviews. Molecular cell biology · 2021Review
- PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation.Nature communications · 2021Article
- A conserved SUMO pathway repairs topoisomerase DNA-protein cross-links by engaging ubiquitin-mediated proteasomal degradation.Science advances · 2020Article
- Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.DNA repair · 2020Review
- Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).DNA repair · 2020Review
- Abortive activity of Topoisomerase I: a challenge for genome integrity?Current genetics · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Reversible topoisomerase I (Top1)-DNA cleavage complexes are the key DNA lesion induced by anticancer camptothecins (CPTs) (e.g. topotecan and irinotecan) as well as structurally perturbed DNAs (e.g. oxidatively damaged, UV-irradiated, or alkylated DNA). It has been proposed that Top1 cleavage complexes arrest advancing replication forks, triggering the formation of DNA double strand breaks (DSBs) because of replication fork runoff at the Top1 cleavage complex sites on the leading strand. In this study, we show that the formation of replication-dependent DSBs requires the ubiquitin-proteasome pathway in CPT-treated cells. First, the proteasome inhibitor MG-132 specifically inhibited CPT-induced but not ionizing radiation- or hydroxyurea-induced DSBs as revealed by both the neutral comet assay and measurements of the specific DNA damage signals (e.g. gamma-H2AX, phosphorylated ataxia telangiectasia mutated (Ser-1981), and phosphorylated Chk2 (Ser-33/35)) that are characteristic for DSBs. Knocking down the 20 S proteasome maturation protein also supported the requirement of the proteasome activity for CPT-induced DSBs. Second, CPT-induced DSB signals were shown to require ubiquitin, ubiquitin-activating enzyme (E1), a CUL-3-based ubiquitin ligase (E3), and the formation of Lys-48-linked polyubiquitin chains on Top1. Third, immunocytochemical studies revealed that the CPT-induced formation of gamma-H2AX foci occurred at the replication forks and was attenuated by co-treatment with the proteasome inhibitor MG-132. In the aggregate, these results support a replication fork collision model in which Top1 cleavage complexes at the arrested replication forks are degraded by proteasome prior to replication fork runoff on the leading strand to generate DSBs.
Indexed as
Identifiers
What OpenQuestion holds
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.