ArticleNucleic acids research2021
Dynamics of the HD regulatory subdomain of PARP-1; substrate access and allostery in PARP activation and inhibition.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Structural basis of PARP2 recognition of nucleosomal DNA breaks and inhibitor trapping.Nucleic acids research · 2026Article
- Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3.Protein & cell · 2026Article
- Comprehensive metabolomic profiling of Egyptian Salvia species reveals promising leads for chemopreventive and anti-inflammatory drug development: In vitro and In silico study.Scientific reports · 2026Article
- A chemoproteomic atlas of the human purine interactome for regioselective ligand discovery.Nature communications · 2026Article
- AI-Enhanced Adaptive Virtual Screening Platform Enabling Exploration of 69 Billion Molecules Discovers Structurally Validated FSP1 Inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Enabling multi-target drug discovery through latent evolutionary optimization and synthesis-aware prioritization (EVOSYNTH).Communications chemistry · 2026Article
- PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation.Nature communications · 2026Article
- The effect of PARP and PLK1 dual inhibition on the expression of important protein signaling pathways, DNA damage, and molecular docking scores against MCF-7 and MDA-MB-231 breast cancer cell lines.Irish journal of medical science · 2026Article
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- Design and Development of DNA Damage Chemical Inducers of Proximity (DD-CIP) for Targeted Cancer Therapy.bioRxiv : the preprint server for biology · 2025Article
- Potent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.RSC advances · 2025Article
- YY1 drives PARP1 expression essential for PARylation of NONO in mRNA maturation during neuroblastoma progression.Journal of translational medicine · 2024Article
- Base editing screens define the genetic landscape of cancer drug resistance mechanisms.Nature genetics · 2024Article
- Targeting PARP-1 and DNA Damage Response Defects in Colorectal Cancer Chemotherapy with Established and Novel PARP Inhibitors.Cancers · 2024Article
- Cooperative nucleic acid binding by Poly ADP-ribose polymerase 1.Scientific reports · 2024Article
- Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks.The Biochemical journal · 2024Article
- A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins.ACS chemical biology · 2024Article
- Structural and biochemical analysis of the PARP1-homology region of PARP4/vault PARP.Nucleic acids research · 2023Article
- Updated protein domain annotation of the PARP protein family sheds new light on biological function.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
PARP-1 is a key early responder to DNA damage in eukaryotic cells. An allosteric mechanism links initial sensing of DNA single-strand breaks by PARP-1's F1 and F2 domains via a process of further domain assembly to activation of the catalytic domain (CAT); synthesis and attachment of poly(ADP-ribose) (PAR) chains to protein sidechains then signals for assembly of DNA repair components. A key component in transmission of the allosteric signal is the HD subdomain of CAT, which alone bridges between the assembled DNA-binding domains and the active site in the ART subdomain of CAT. Here we present a study of isolated CAT domain from human PARP-1, using NMR-based dynamics experiments to analyse WT apo-protein as well as a set of inhibitor complexes (with veliparib, olaparib, talazoparib and EB-47) and point mutants (L713F, L765A and L765F), together with new crystal structures of the free CAT domain and inhibitor complexes. Variations in both dynamics and structures amongst these species point to a model for full-length PARP-1 activation where first DNA binding and then substrate interaction successively destabilise the folded structure of the HD subdomain to the point where its steric blockade of the active site is released and PAR synthesis can proceed.
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