ArticleOncotarget2017
UV-induced proteolysis of RNA polymerase II is mediated by VCP/p97 segregase and timely orchestration by Cockayne syndrome B protein.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions.Nucleic acids research · 2025Article
- Multiple Forms and Functions of Premature Termination by RNA Polymerase II.Journal of molecular biology · 2025Review
- Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity.Nucleic acids research · 2024Article
- DNA break induces rapid transcription repression mediated by proteasome-dependent RNAPII removal.Cell reports · 2024Article
- Chromatin damage generated by DNA intercalators leads to degradation of RNA Polymerase II.Nucleic acids research · 2024Article
- New Discoveries on Protein Recruitment and Regulation during the Early Stages of the DNA Damage Response Pathways.International journal of molecular sciences · 2024Review
- Live-cell imaging of endogenous CSB-mScarletI as a sensitive marker for DNA-damage-induced transcription stress.Cell reports methods · 2024Article
- RNAPII response to transcription-blocking DNA lesions in mammalian cells.The FEBS journal · 2023Review
- Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast.The EMBO journal · 2023Article
- Cooperative assembly of p97 complexes involved in replication termination.Nature communications · 2022Article
- Review
- DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II.Nature communications · 2022Article
- SPT5 stabilization of promoter-proximal RNA polymerase II.Molecular cell · 2021Article
- Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Timely upstream events regulating nucleotide excision repair by ubiquitin-proteasome system: ubiquitin guides the way.DNA repair · 2021Review
- A Role for VCP/p97 in the Processing of Drug-Stabilized TOP2-DNA Covalent Complexes.Molecular pharmacology · 2021Article
- Dissecting regulatory pathways for transcription recovery following DNA damage reveals a non-canonical function of the histone chaperone HIRA.Nature communications · 2021Article
- Current and emerging roles of Cockayne syndrome group B (CSB) protein.Nucleic acids research · 2021Review
- Spironolactone-induced XPB degradation requires TFIIH integrity and ubiquitin-selective segregase VCP/p97.Cell cycle (Georgetown, Tex.) · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
RNA polymerase II (RNAPII) acts as a damage sensor for transcription-coupled nucleotide excision repair (TC-NER) and undergoes proteolytic clearance from damaged chromatin by the ubiquitin-proteasome system (UPS). Here, we report that Valosin-containing protein (VCP)/p97, a druggable oncotarget, is essential for RNAPII's proteolytic clearance in mammalian cells. We show that inhibition of VCP/p97, or siRNA-mediated ablation of VCP/p97 and its cofactors UFD1 and UBXD7 severely impairs ultraviolet radiation (UVR)-induced RNAPII degradation. VCP/p97 interacts with RNAPII, and the interaction is enhanced by Cockayne syndrome B protein (CSB). However, the VCP/p97-mediated RNAPII proteolysis occurs independent of CSB. Surprisingly, CSB enhances UVR-induced RNAPII ubiquitination but delays its turnover. Additionally, VCP/p97-mediated RNAPII turnover occurs with and without Von Hippel-Lindau tumor suppressor protein (pVHL), a known substrate receptor of Elongin E3 ubiquitin ligase for RNAPII. Moreover, pVHL re-expression improves cell viability following UVR. Whereas, VCP/p97 inhibition decreases cell viability and enhances a low-dose UVR killing in presence of pVHL. These findings reveal a function of VCP/p97 segregase in UVR-induced RNAPII degradation in mammalian cells, and suggest a role of CSB in coordinating VCP/p97-mediated extraction of ubiquitinated RNAPII and CSB itself from chromatin.
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