ArticleScience advances2024
EZH2 directly methylates PARP1 and regulates its activity in cancer.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Beyond the dose: a clearance-enabled in vitro platform for evaluating local therapies.Drug delivery and translational research · 2026Article
- Bipolar Androgen Therapy as a Potential Mechanistic Bridge to Enhance PARP Inhibitor Efficacy in Prostate Cancer.The Kaohsiung journal of medical sciences · 2026Article
- Silica based nanocarriers for combination immunotherapy targeting the tumor immune microenvironment.Drug delivery and translational research · 2026Review
- Integrating network toxicology with multi-omics approaches to elucidate molecular targets and pathway mechanisms in BPA-induced hepatocellular carcinoma.Molecular diversity · 2026Article
- 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
- Cancer metabolism in radiation sensitization - complementary roles of O-GlcNAc transferase and PARP1.Journal of cell science · 2026Article
- The mitochondrial translocation of phosphorylated EZH2 promotes PARP inhibitor resistance in BRCA1-deficient epithelial ovarian cancer.Cell discovery · 2026Article
- Targeting the TRIM28-EZH2 Protein-Protein Interface With Cysteine-Reactive Covalent Inhibitors: A Computational Blueprint for Cancer Therapy.Chemistry & biodiversity · 2026Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
DNA repair dysregulation is a key driver of cancer development. Understanding the molecular mechanisms underlying DNA repair dysregulation in cancer cells is crucial for cancer development and therapies. Here, we report that enhancer of zeste homolog 2 (EZH2) directly methylates poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1), an essential enzyme involved in DNA repair, and regulates its activity. Functionally, EZH2-catalyzed methylation represses PARP1 catalytic activity, down-regulates the recruitment of x-ray repair cross-complementing group-1 to DNA lesions and its associated DNA damage repair; on the other hand, it protects the cells from nicotinamide adenine dinucleotide overconsumption upon DNA damage formation. Meanwhile, EZH2-mediated methylation regulates PARP1 transcriptional and oncogenic activity, at least in part, through impairing PARP1-E2F1 interaction and E2F1 transcription factor activity. EZH2 and PARP1 inhibitors synergistically suppress prostate cancer growth. Collectively, our findings uncover an insight of EZH2 functions in fine-tuning PARP1 activity during DNA damage repair and cancer progression, which provides a rationale for combinational targeting EZH2 and PARP1 in cancer.
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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.