ArticleNature cell biology2022
Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase separation to inhibit global transcription after DNA damage.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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Who cites it
46 citing papers in PubMed.
- The ADP-ribosyltransferases 3 (ART3) is a novel suppressor of pathological cardiac hypertrophy by ribosylating ITGA7.Acta pharmaceutica Sinica. B · 2026Article
- Oxidative stress triggers RNAPII arrest through PARylation and DNA damage.Nature communications · 2026Article
- NAT10-mediated crosstalk between acetylation and PARylation enhances the function of PARP1 promoting primary resistance in esophageal cancer.Cellular and molecular life sciences : CMLS · 2026Article
- Stabilization of AFF1 by PARylation ensures transcriptional restart after DNA damage.Nature chemical biology · 2026Article
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- PIK3CA Mutations Downregulate PPT1 to Promote Adipogenesis by Suppressing P300 Depalmitoylation and Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cathepsin E drives colorectal cancer progression and immune evasion via ZNF326 ADP-ribosylation and TGF-β/SMAD activation.Journal of translational medicine · 2026Article
- R-loops orchestrate RNAPII transcriptional reprogramming for the maternal-to-zygotic transition.Cell research · 2026Article
- Review
- Liquid-Liquid Phase Separation in Cancer Drug Resistance: Mechanisms and Therapeutic Opportunities.Oncology research · 2026Review
- Transcription-coupled repair: tangled up in convoluted repair.The FEBS journal · 2025Review
- Poly (ADP-ribose) polymerase in yeasts: characterization and involvement in telomere maintenance.Nucleic acids research · 2025Article
- MLKL PARylation in the endothelial niche triggers angiocrine necroptosis to evade cancer immunosurveillance and chemotherapy.Nature cell biology · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- MRPL21-PARP1 axis promotes cisplatin resistance in head and neck squamous cell carcinoma by inhibiting autophagy through the PI3K/AKT/mTOR signaling pathway.Journal of experimental & clinical cancer research : CR · 2025Article
- Therapeutic advances and application of PARP inhibitors in breast cancer.Translational oncology · 2025Review
- Article
- Interplay and Dynamics of Chromatin Architecture and DNA Damage Response: An Overview.Cancers · 2025Review
- Transcription regulation by biomolecular condensates.Nature reviews. Molecular cell biology · 2025Review
- PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications.Trends in biochemical sciences · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
DNA damage shuts down genome-wide transcription to prevent transcriptional mutagenesis and to initiate repair signalling, but the mechanism to stall elongating RNA polymerase II (Pol II) is not fully understood. Central to the DNA damage response, poly(ADP-ribose) polymerase 1 (PARP1) initiates DNA repair by translocating to the lesions where it catalyses protein poly(ADP-ribosylation). Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. This prevents CycT1 from undergoing liquid-liquid phase separation that is required for CDK9 to hyperphosphorylate Pol II and to stimulate elongation. Functionally, poly(ADP-ribosylation) of CycT1 promotes DNA repair and cell survival. Thus, the P-TEFb-PARP1 signalling plays a protective role in transcription quality control and genomic stability maintenance after DNA damage.
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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.