ArticleMolecular cell2015
Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1.
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 211 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
211 citing papers in PubMed, 1 synthesis or guideline pooled it, 322 citations in OpenAlex.
- Safety and tolerability of PARP inhibitors in cancer patients: a network meta-analysis of randomized controlled trials.BMC cancer · 2026Pooled it
- NADRSC chemical biology · 2026Review
- Structural basis of PARP2 recognition of nucleosomal DNA breaks and inhibitor trapping.Nucleic acids research · 2026Article
- CAF-1 in Replication and Repair: A Critical Genetic Mediator of Synthesis-Coupled Nucleosome Assembly.Biomolecules · 2026Review
- The BRCT domain enhances DNA binding and catalytic efficiency of fungal PARPs.Nature communications · 2026Article
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Tirapazamine sensitises hypoxic homologous recombination-proficient NSCLC to PARP inhibition.Cell death discovery · 2026Article
- Identifying potential binding sites for complex formation between Tyrosyl-DNA phosphodiesterase 1 and poly [ADP-ribose] polymerase 1.Physical chemistry chemical physics : PCCP · 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
- Comparative Assessment of Free Energy Computational Methods for Revealing the Interactions Driving PARP1 Selective Inhibition.Journal of chemical information and modeling · 2026Article
- Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity.PLoS computational biology · 2026Article
- Differential proteomic responses to short-term heat stress in Vechur and crossbred cattle of Kerala.Tropical animal health and production · 2026Article
- PARP-2 catalytic activity drives replication-ICL repair in an allele-specific manner during germline development.PLoS genetics · 2026Article
- Time-Resolved Single-Molecule FRET Reveals Length-Dependent Nucleosome Decompaction by Poly(ADP-ribose).bioRxiv : the preprint server for biology · 2026Article
- PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation.Nature communications · 2026Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- Unraveling the Resistance: Challenges and Advances in PARP Inhibitor Therapy for BRCA1/2 Breast Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- The lncRNA PARylator promotes PARP1 activation and resistance to DNA‑damaging therapy in esophageal squamous cell carcinoma.Experimental hematology & oncology · 2025Article
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- The zinc finger domains of PARP-1 are selectively and potently inhibited by the Au(I)-based drugs sodium aurothiomalate and aurothioglucose.FEBS letters · 2025Article
151 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Poly(ADP-ribose)polymerase 1 (PARP-1) is a key eukaryotic stress sensor that responds in seconds to DNA single-strand breaks (SSBs), the most frequent genomic damage. A burst of poly(ADP-ribose) synthesis initiates DNA damage response, whereas PARP-1 inhibition kills BRCA-deficient tumor cells selectively, providing the first anti-cancer therapy based on synthetic lethality. However, the mechanism underlying PARP-1's function remained obscure; inherent dynamics of SSBs and PARP-1's multi-domain architecture hindered structural studies. Here we reveal the structural basis of SSB detection and how multi-domain folding underlies the allosteric switch that determines PARP-1's signaling response. Two flexibly linked N-terminal zinc fingers recognize the extreme deformability of SSBs and drive co-operative, stepwise self-assembly of remaining PARP-1 domains to control the activity of the C-terminal catalytic domain. Automodification in cis explains the subsequent release of monomeric PARP-1 from DNA, allowing repair and replication to proceed. Our results provide a molecular framework for understanding PARP inhibitor action and, more generally, allosteric control of dynamic, multi-domain proteins.
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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.