ArticleNucleic acids research2016
Poly(ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- PAF1c depletion confers chemoresistance to topoisomerase inhibitors.Cell insight · 2026Article
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.Nature communications · 2026Article
- AAV Kills Dividing Cells by Depleting PARP1 and Other DNA Damage Response Proteins.bioRxiv : the preprint server for biology · 2025Article
- Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy.Scientific reports · 2025Article
- Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review).Molecular and clinical oncology · 2025Review
- Excessive MYC-topoisome activity triggers acute DNA damage, MYC degradation, and replacement by a p53-topoisome.Molecular cell · 2024Article
- Poly(ADP-Ribose) Polymerase (PARP) Inhibitors for Cancer Therapy: Advances, Challenges, and Future Directions.Biomolecules · 2024Review
- RNA interacts with topoisomerase I to adjust DNA topology.Molecular cell · 2024Article
- TDP1 phosphorylation by CDK1 in mitosis promotes MUS81-dependent repair of trapped Top1-DNA covalent complexes.The EMBO journal · 2024Article
- PARP1-dependent DNA-protein crosslink repair.Nature communications · 2024Article
- Transcriptomic Analysis of CRISPR/Cas9-Mediated PARP1-Knockout Cells under the Influence of Topotecan and TDP1 Inhibitor.International journal of molecular sciences · 2023Article
- A literature review of the promising future ofAnnals of translational medicine · 2022Review
- Topoisomerase 1-dependent R-loop deficiency drives accelerated replication and genomic instability.Cell reports · 2022Article
- Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer.Aging cell · 2022Article
- MYC assembles and stimulates topoisomerases 1 and 2 in a "topoisome".Molecular cell · 2022Article
- Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs.Oncology and therapy · 2021Article
- PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation.Nature communications · 2021Article
- The role of Trop2 in prostate cancer: an oncogene, biomarker, and therapeutic target.American journal of clinical and experimental urology · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Topoisomerase 1 (Top1) is essential for removing the DNA supercoiling generated during replication and transcription. Anticancer drugs like camptothecin (CPT) and its clinical derivatives exert their cytotoxicity by reversibly trapping Top1 in covalent complexes on the DNA (Top1cc). Poly(ADP-ribose) polymerase (PARP) catalyses the addition of ADP-ribose polymers (PAR) onto itself and Top1. PARP inhibitors enhance the cytotoxicity of CPT in the clinical trials. However, the molecular mechanism by which PARylation regulates Top1 nuclear dynamics is not fully understood. Using live-cell imaging of enhanced green fluorescence tagged-human Top1, we show that PARP inhibitors (Veliparib, ABT-888) delocalize Top1 from the nucleolus to the nucleoplasm, which is independent of Top1-PARP1 interaction. Using fluorescence recovery after photobleaching and subsequent fitting of the data employing kinetic modelling we demonstrate that ABT-888 markedly increase CPT-induced bound/immobile fraction of Top1 (Top1cc) across the nuclear genome, suggesting Top1-PARylation counteracts CPT-induced stabilization of Top1cc. We further show Trp205 and Asn722 of Top1 are critical for subnuclear dynamics. Top1 mutant (N722S) was restricted to the nucleolus in the presence of CPT due to its deficiency in the accumulation of CPT-induced Top1-PARylation and Top1cc formation. This work identifies ADP-ribose polymers as key determinant for regulating Top1 subnuclear dynamics.
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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.