ArticleNucleic acids research2020
Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
- Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.Nucleic acids research · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- PARP1 regulates the genomic ribonucleotide processing activity of TOP1 to prevent the formation of toxic TOP1-DNA adducts and the associated mutations.bioRxiv : the preprint server for biology · 2026Article
- Versatile and sensitive detection of mono- and poly(ADP-ribosyl)ation reveals XRCC1-dependent remodelling of PARP1 signalling.Nature communications · 2026Article
- Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor.Cell reports methods · 2026Article
- Nucleosome unwrapping and PARP1 allostery drive affinities for chromatin and DNA breaks.Nature communications · 2025Article
- Measuring PARP1 mobility at DNA damage sites by segmented fluorescence correlation spectroscopy.Biophysical journal · 2025Article
- Joining of DNA breaks- interplay between DNA ligases and poly (ADP-ribose) polymerases.DNA repair · 2025Review
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates.Cell death and differentiation · 2025Article
- Article
- XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites.Nucleic acids research · 2025Article
- The interplay between DNA damage response and mitochondrial dysfunction in radiotherapy.Frontiers in oncology · 2025Review
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- EZH2 directly methylates PARP1 and regulates its activity in cancer.Science advances · 2024Article
- Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts.Molecular cell · 2024Article
- Poly(ADP-Ribose) Polymerase (PARP) Inhibitors for Cancer Therapy: Advances, Challenges, and Future Directions.Biomolecules · 2024Review
- NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion.Molecular cancer research : MCR · 2024Article
- Redundant but essential functions of PARP1 and PARP2 in DNA ligase I-independent DNA replication.Nucleic acids research · 2024Article
- Monitoring nucleolar-nucleoplasmic protein shuttling in living cells by high-content microscopy and automated image analysis.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA breaks recruit and activate PARP1/2, which deposit poly-ADP-ribose (PAR) to recruit XRCC1-Ligase3 and other repair factors to promote DNA repair. Clinical PARP inhibitors (PARPi) extend the lifetime of damage-induced PARP1/2 foci, referred to as 'trapping'. To understand the molecular nature of 'trapping' in cells, we employed quantitative live-cell imaging and fluorescence recovery after photo-bleaching. Unexpectedly, we found that PARP1 exchanges rapidly at DNA damage sites even in the presence of clinical PARPi, suggesting the persistent foci are not caused by physical stalling. Loss of Xrcc1, a major downstream effector of PAR, also caused persistent PARP1 foci without affecting PARP1 exchange. Thus, we propose that the persistent PARP1 foci are formed by different PARP1 molecules that are continuously recruited to and exchanging at DNA lesions due to attenuated XRCC1-LIG3 recruitment and delayed DNA repair. Moreover, mutation analyses of the NAD+ interacting residues of PARP1 showed that PARP1 can be physically trapped at DNA damage sites, and identified H862 as a potential regulator for PARP1 exchange. PARP1-H862D, but not PARylation-deficient PARP1-E988K, formed stable PARP1 foci upon activation. Together, these findings uncovered the nature of persistent PARP1 foci and identified NAD+ interacting residues involved in the PARP1 exchange.
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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.