ArticleMolecular cell2015
PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
What it found
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Who cites it
182 citing papers in PubMed, 345 citations in OpenAlex.
- NADRSC chemical biology · 2026Review
- Structural basis of PARP2 recognition of nucleosomal DNA breaks and inhibitor trapping.Nucleic acids research · 2026Article
- Effects of a cancer-associated mutation and multiple serine phosphorylation on poly(ADP-ribose) polymerase 2.Biophysical journal · 2026Article
- The BRCT domain enhances DNA binding and catalytic efficiency of fungal PARPs.Nature communications · 2026Article
- PARP1 Exhibits an Enzymatically Inactive Chromatin Binding Mode.bioRxiv : the preprint server for biology · 2026Article
- From mutation to treatment: The dual role of BRCA1 and BRCA2 in gynecological malignancy development and management a systematic review.Biochemistry and biophysics reports · 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
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- PROTAC-based synthetic lethality strategy endogenously activates systemic STING to boost antitumor immunity.Science advances · 2026Article
- PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation.Nature communications · 2026Article
- Article
- MicroRNA-based strategies to overcome the immunotherapy barrier in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- Synthesis, Anticancer Evaluation, and Molecular Docking of Triazolylmethyl-Dihydroquinazolinyl Benzoate Derivatives as Potential PARP-1 Inhibitors.Chemistry & biodiversity · 2026Article
- PARP1 and PARylation facilitate transcription-coupled DNA repair by stabilizing the CSB-RNAPII complex.Nucleic acids research · 2025Article
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- A Population-Specific PARP1 Gene Variation Modulates PARP Trapping.bioRxiv : the preprint server for biology · 2025Article
- Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15.Nature communications · 2025Article
- Histone PARylation factor 1: a review of its role in the DNA damage response.Nucleic acids research · 2025Review
- PARP enzyme synthesis of protein-free poly(ADP-ribose): Implications for DNA damage signaling and repair.DNA repair · 2025Review
122 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is associated with cell death. The mechanism for tight control of the robust catalytic potential of PARP-1 remains unclear. By monitoring PARP-1 dynamics using hydrogen/deuterium exchange-mass spectrometry (HXMS), we unexpectedly find that a specific portion of the helical subdomain (HD) of the catalytic domain rapidly unfolds when PARP-1 encounters a DNA break. Together with biochemical and crystallographic analysis of HD deletion mutants, we show that the HD is an autoinhibitory domain that blocks productive NAD(+) binding. Our molecular model explains how PARP-1 DNA damage detection leads to local unfolding of the HD that relieves autoinhibition, and has important implications for the design of PARP inhibitors.
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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.