ArticleNature communications2021
PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- Arabidopsis WSS1A, a DNA-protein crosslink repair protease, delays leaf senescence in cooperation with SUMO3.The Plant journal : for cell and molecular biology · 2026Article
- Ubiquitin's code: UPS orchestrating DNA repair and genomic stability under genotoxic stress.Molecular and cellular biochemistry · 2026Review
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- PARP1 trapping activates ATM-mediated NF-κB signaling independent of replication in response to TOP1 blockade.Nucleic acids research · 2026Article
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression.The Journal of clinical investigation · 2026Article
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- OGG1 and MUTYH DNA Glycosylases, the Dynamic Duo Against 8-Oxoguanine DNA Lesion: Structure, Regulation, and Novel Emerging Roles.Biomolecules · 2026Review
- Visualizing DNA repair factor recruitment at sites of transcription in single cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026Article
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- Loss-of-function genetic screen unveils synergistic efficacy of PARG inhibition with combined 5-fluorouracil and irinotecan treatment in colorectal cancer.Clinical and translational medicine · 2025Article
- Article
- PARylation promotes acute kidney injuryActa pharmaceutica Sinica. B · 2025Article
- Topoisomerase IIIα controls alternative lengthening of telomeres.Cell reports · 2025Article
- Epigenetic control of topoisomerase 1 activity presents a cancer vulnerability.Nature communications · 2025Article
- Article
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- TOP1 Mutations and Cross-Resistance to Antibody-Drug Conjugates in Patients with Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- In vitro-in silico analysis reveals that loss of tankyrase1/2 improves bile acid handling in genetically engineered HepG2 cultures.Archives of toxicology · 2025Article
- Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.Science advances · 2025Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Poly(ADP)-ribosylation (PARylation) regulates chromatin structure and recruits DNA repair proteins. Using single-molecule fluorescence microscopy to track topoisomerase I (TOP1) in live cells, we found that sustained PARylation blocked the repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) in a similar fashion as inhibition of the ubiquitin-proteasome system (UPS). PARylation of TOP1-DPC was readily revealed by inhibiting poly(ADP-ribose) glycohydrolase (PARG), indicating the otherwise transient and reversible PARylation of the DPCs. As the UPS is a key repair mechanism for TOP1-DPCs, we investigated the impact of TOP1-DPC PARylation on the proteasome and found that the proteasome is unable to associate with and digest PARylated TOP1-DPCs. In addition, PARylation recruits the deubiquitylating enzyme USP7 to reverse the ubiquitylation of PARylated TOP1-DPCs. Our work identifies PARG as repair factor for TOP1-DPCs by enabling the proteasomal digestion of TOP1-DPCs. It also suggests the potential regulatory role of PARylation for the repair of a broad range of DPCs.
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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.