ArticleNature cell biology2022
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 158 citations in OpenAlex.
- PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer.Nature communications · 2026Article
- PARP1 rewires neuroinflammatory and redox metabolism associated with reactive neuroglia in neuropathic pain.Redox biology · 2026Article
- ROS-ATM-CBP axis-mediated PARP1 lactylation aggravates doxorubicin-induced cardiotoxicity.Clinical and translational medicine · 2026Article
- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- The nuclear shredder behind PARPi resistance.Nature cell biology · 2026Article
- The interaction between virus-bound KLF4 and host-bound PARP1 directs the localization of wild-type adeno-associated virus type 2 (wtAAV2) to cellular sites of DNA damage.Journal of virology · 2026Article
- DAXX promotes SUMOylation of chromatin-trapped DNMT1.Journal of biochemistry · 2026Article
- PARP1-BCAT2 axis upregulates ABCG1 via histone lactylation to drive acquired PARP inhibitor resistance in prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Dysregulated nuclear Lamin B1 in DYT1 dystonia thickens nuclear lamina and disrupts 14-3-3 proteins.Cell death discovery · 2026Article
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- Article
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy.Frontiers in genetics · 2026Review
- Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer.Oncology research · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Non-covalent SUMO interactions with ligases and effectors: SUMO-interacting motifs and beyond.Essays in biochemistry · 2025Review
- DNA double strand break repair: a model of specificity and complexity in SUMO signalling.Essays in biochemistry · 2025Review
- METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using wild-type and a trapping-deficient PARP1 mutant combined with rapid immunoprecipitation mass spectrometry of endogenous proteins and Apex2 proximity labelling, we delineated mass spectrometry-based interactomes of trapped and non-trapped PARP1. These analyses identified an interaction between trapped PARP1 and the ubiquitin-regulated p97 ATPase/segregase. We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. Small-molecule p97-complex inhibitors, including a metabolite of the clinically used drug disulfiram (CuET), prolonged PARP1 trapping and enhanced PARP inhibitor-induced cytotoxicity in homologous recombination-defective tumour cells and patient-derived tumour organoids. Together, these results suggest that p97 ATPase plays a key role in the processing of trapped PARP1 and the response of tumour cells to PARP inhibitors.
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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.