ArticleScience advances2023
Clinical PARP inhibitors allosterically induce PARP2 retention on DNA.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- 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
- PARP inhibitor YCH1899 activates type I interferon signaling and synergizes with STING agonists in BRCA-proficient tumors.Molecular biomedicine · 2026Article
- PARP1 trapping activates ATM-mediated NF-κB signaling independent of replication in response to TOP1 blockade.Nucleic acids research · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Experimental and Mechanistic Validation of PARP1pred for Identifying Potent Leads.Computational and structural biotechnology journal · 2026Article
- Synergistic nanomedicine overcomes hypoxia-driven DNA repair to potentiate radiotherapy for lung adenocarcinoma.Theranostics · 2026Article
- From dual inhibition to precision selectivity: the molecular rationale and clinical evolution of next-generation PARP1-selective inhibitors in solid tumors.Frontiers in oncology · 2026Review
- Nucleosome unwrapping and PARP1 allostery drive affinities for chromatin and DNA breaks.Nature communications · 2025Article
- A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.Genome biology · 2025Article
- H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition.Neuro-oncology · 2025Article
- Targeting the proliferation of glioblastoma cells and enhancement of doxorubicin and temozolomide cytotoxicity through inhibition of PFKFB4 and HMOX1 genes with siRNAs.Scientific reports · 2025Article
- Isoform-specific function of NSD3 in DNA replication stress confers resistance to PARP inhibitors in prostate cancer.Molecular cell · 2025Article
- Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer.Cellular and molecular life sciences : CMLS · 2025Article
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Joining of DNA breaks- interplay between DNA ligases and poly (ADP-ribose) polymerases.DNA repair · 2025Review
- A PARP2 active site helix melts to permit DNA damage-induced enzymatic activation.Molecular cell · 2025Article
- XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites.Nucleic acids research · 2025Article
- Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.Current pharmaceutical biotechnology · 2025Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
PARP1 and PARP2 detect DNA breaks, which activates their catalytic production of poly(ADP-ribose) that recruits repair factors and contributes to PARP1/2 release from DNA. PARP inhibitors (PARPi) are used in cancer treatment and target PARP1/2 catalytic activity, interfering with repair and increasing PARP1/2 persistence on DNA damage. In addition, certain PARPi exert allosteric effects that increase PARP1 retention on DNA. However, no clinical PARPi exhibit this allosteric behavior toward PARP1. In contrast, we show that certain clinical PARPi exhibit an allosteric effect that retains PARP2 on DNA breaks in a manner that depends on communication between the catalytic and DNA binding regions. Using a PARP2 mutant that mimics an allosteric inhibitor effect, we observed increased PARP2 retention at cellular damage sites. The PARPi AZD5305 also exhibited a clear reverse allosteric effect on PARP2. Our results can help explain the toxicity of clinical PARPi and suggest ways to improve PARPi moving forward.
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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.