{"entity": "researcher", "timestamp": "2026-08-20T21:14:52.907Z", "family": "Yu", "given": "Lu", "initials": "L", "orcid": "0000-0001-8378-9112", "affiliations": ["Functional Proteomics Laboratory, The Institute of Cancer Research, London, UK."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ec4d01c279c4832b1ab56a4f320eee8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ec4d01c279c4832b1ab56a4f320eee8"}}, "publications": [{"entity": "publication", "iuid": "de99bd23773f44238396a27f3a1b6ebd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/de99bd23773f44238396a27f3a1b6ebd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/de99bd23773f44238396a27f3a1b6ebd"}}, "title": "The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.", "authors": [{"family": "Krastev", "given": "Dragomir B", "initials": "DB", "orcid": "0000-0003-4298-7272", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/747053a378e84ace83d2e393a33b9057.json"}}, {"family": "Li", "given": "Shudong", "initials": "S"}, {"family": "Sun", "given": "Yilun", "initials": "Y", "orcid": "0000-0002-6249-2704", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8009a43c7e746ec87c3f2b985588abb.json"}}, {"family": "Wicks", "given": "Andrew J", "initials": "AJ", "orcid": "0000-0002-9307-3262", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3dcc68fbb1bb49bd9ec7799d436694b3.json"}}, {"family": "Hoslett", "given": "Gwendoline", "initials": "G", "orcid": "0000-0002-0030-7761", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2f847d4850d544249876cb89f1c82fa1.json"}}, {"family": "Weekes", "given": "Daniel", "initials": "D"}, {"family": "Badder", "given": "Luned M", "initials": "LM"}, {"family": "Knight", "given": "Eleanor G", "initials": "EG"}, {"family": "Marlow", "given": "Rebecca", "initials": "R"}, {"family": "Pardo", "given": "Mercedes Calvo", "initials": "MC", "orcid": "0000-0002-3477-9695", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3e5a95e3b8864357b98c6024af9974ed.json"}}, {"family": "Yu", "given": "Lu", "initials": "L", "orcid": "0000-0001-8378-9112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ec4d01c279c4832b1ab56a4f320eee8.json"}}, {"family": "Talele", "given": "Tanaji T", "initials": "TT"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Choudhary", "given": "Jyoti S", "initials": "JS", "orcid": "0000-0003-0881-5477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea9f0b1f3188478d911447702c316243.json"}}, {"family": "Pommier", "given": "Yves", "initials": "Y"}, {"family": "Pettitt", "given": "Stephen J", "initials": "SJ", "orcid": "0000-0003-3313-3857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3e9e060345c4bc681d3deab751adf41.json"}}, {"family": "Tutt", "given": "Andrew N J", "initials": "ANJ", "orcid": "0000-0001-8715-2901", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c1324094ed43453a9e953a46c486a269.json"}}, {"family": "Ramadan", "given": "Kristijan", "initials": "K", "orcid": "0000-0001-5522-021X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/889d31d5e8b24bc0872c26bd387faccd.json"}}, {"family": "Lord", "given": "Christopher J", "initials": "CJ", "orcid": "0000-0002-3226-0515", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ff9fc23cf0c94cd09ae6b58a68707e84.json"}}], "type": "journal article", "published": "2022-01-00", "journal": {"title": "Nat. Cell Biol.", "issn": "1476-4679", "volume": "24", "issue": "1", "pages": "62-73", "issn-l": "1465-7392"}, "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.", "doi": "10.1038/s41556-021-00807-6", "pmid": "35013556", "labels": [], "xrefs": [{"db": "mid", "key": "EMS138001"}, {"db": "pmc", "key": "PMC8760077"}, {"db": "pii", "key": "10.1038/s41556-021-00807-6"}], "notes": [], "created": "2026-08-20T08:54:53.445Z", "modified": "2026-08-20T08:54:53.832Z"}]}