ArticleGenes & development2019
WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks.
Article in Genes & development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 111 citations in OpenAlex.
- Cellular stress triggers degradation and global redistribution of RNAPII.Science advances · 2026Article
- Cleavage of the RNA polymerase II general transcription factor TFIIB tunes transcription during stress.Genes & development · 2026Article
- K63-linked ubiquitylation of S2P-RNAPII regulates transcription in a DNAPK inter-dependent manner in response to double-strand breaks.Nucleic acids research · 2026Article
- LMO7-mediated POLR2A degradation promotes cellular senescence through the MDM4/p53/p21 axis.Cell death & disease · 2026Article
- WWP2 in immune surveillance and antigen presentation: context-dependent roles in B cells, T cells, and tumor immune escape.Frontiers in immunology · 2026Review
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Identification of human RNA Polymerase II interactors at early stages of transcription.bioRxiv : the preprint server for biology · 2025Article
- Herpes simplex virus type 1 reshapes host chromatin architecture via transcription machinery hijacking.Nature communications · 2025Article
- Exploration of genes related to the development of cancer of unknown primary.Oncology reports · 2025Article
- WWP2 deletion aggravates acute kidney injury by targeting CDC20/autophagy axis.Journal of advanced research · 2025Article
- DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.Cellular & molecular biology letters · 2025Review
- DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.Nature communications · 2025Article
- Traffic light at DSB-transit regulation between gene transcription and DNA repair.FEBS letters · 2025Review
- Transcription-coupled DNA repair protects genome stability upon oxidative stress-derived DNA strand breaks.FEBS letters · 2025Review
- Article
- DNA break induces rapid transcription repression mediated by proteasome-dependent RNAPII removal.Cell reports · 2024Article
- Transcriptional inhibition after irradiation occurs preferentially at highly expressed genes in a manner dependent on cell cycle progression.bioRxiv : the preprint server for biology · 2024Article
- DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.Cell systems · 2024Article
- Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells.Scientific reports · 2024Article
- IN-DEPTH MAPPING OF DNA-PKcs SIGNALING UNCOVERS CONSERVED FEATURES OF ITS KINASE SPECIFICITY.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA double-strand breaks (DSBs) at RNA polymerase II (RNAPII) transcribed genes lead to inhibition of transcription. The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in transcription inhibition at DSBs by stimulating proteasome-dependent eviction of RNAPII at these lesions. How DNA-PK triggers RNAPII eviction to inhibit transcription at DSBs remains unclear. Here we show that the HECT E3 ubiquitin ligase WWP2 associates with components of the DNA-PK and RNAPII complexes and is recruited to DSBs at RNAPII transcribed genes. In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII. The lack of WWP2 or expression of nonubiquitylatable RPB1 abrogates the binding of nonhomologous end joining (NHEJ) factors, including DNA-PK and XRCC4/DNA ligase IV, and impairs DSB repair. These findings suggest that WWP2 operates in a DNA-PK-dependent shutoff circuitry for RNAPII clearance that promotes DSB repair by protecting the NHEJ machinery from collision with the transcription machinery.
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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.