STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading
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Abstract
Transcription-coupled repair (TCR) is the major pathway to remove transcription-blocking lesions. Although discovered for nearly 40 years, the mechanism and critical players of mammalian TCR remain unclear. STK19 is a factor affecting cell survival and recovery of RNA synthesis in response to DNA damage, however, whether it is a necessary component for TCR is unknown. Here, we demonstrated that STK19 is essential for human TCR. Mechanistically, STK19 is recruited to damage sites through direct interaction with CSA. It can also interact with RNA polymerase II in vitro. Once recruited, STK19 plays an important role in UVSSA ubiquitination which is needed for TCR. STK19 also promotes TCR independent of UVSSA ubiquitination by stimulating TFIIH recruitment through its direct interaction with TFIIH. In summary, our results suggest that STK19 is a key factor of human TCR that links CSA, UVSSA ubiquitination and TFIIH loading, shedding light on the molecular mechanisms of TCR.
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Cites
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“Although TCR was first discovered in mammalian cells nearly 40 years ago ( 61 ), the molecular mechanism of mammalian TCR still remains unclear.”
ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation
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Flagged first, then by citations
- Authors
- Tan, Y., Gao, M., Huang, Y., Zhan, D., Wu, S., An, J., Zhang, X., & Hu, J.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Hu, Jinchuan
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-10-02
- Volume
- 52
- Issue
- 21
- Pages
- 12767-12783
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC11602130
- OpenAlex
- W4403013225
- Cited by
- 31
- References
- 8
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 4
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Key R&D Program of China (2022YFA1303000)
- National Natural Science Foundation of China (32271343)
- Shanghai Municipal Natural Science Foundation (22ZR1413900)
- university in Shanghai
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- transcription-coupled repair, CSA, RNA polymerase II, DNA damage response, UV-induced DNA damage, protein-protein interaction
- MeSH terms
- Excision Repair, Carrier Proteins, DNA Damage, DNA Repair, DNA Helicases, DNA-Binding Proteins, Humans, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Protein Serine-Threonine Kinases, Transcription Factor TFIIH, Ubiquitination, HEK293 Cells
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