PreprintCited by 31DNA Repair MechanismsGenomics and Chromatin DynamicsNuclear Structure and Function

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STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading

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Tan, Yuanqing, Gao, Meng, Huang, Yanchao, Zhan, Delin, Wu, Sizhong, An, Jiao, Zhang, Xiping, Hu, Jinchuan·2024·Nucleic Acids Research

Preprint — published as 10.1093/nar/gkae787 · Paper page

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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Metadata

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
openRxiv
Published
2024-07-18
Volume
52
Issue
21
Pages
12767-12783
ISSN
0305-1048 (ISSN-L)
OpenAlex
W4403013225
Cited by
31
References
1
Citations by year
2026: 12 · 2025: 15 · 2024: 4
FWCI
4.21
Type
journal article
Language
en
Open access
Licence
cc-by-nc
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
  • Natural Science Foundation of Shanghai (22ZR1413900)
  • National Natural Science Foundation of China (32271343)
  • National Key Research and Development Program of China (2022YFA1303000)
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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