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Peer-reviewedCC BYMolecular Cell

STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment

  • Anisha Ramadhin
  • Shun-Hsiao Lee
  • Di Zhou
  • Anita Salmazo
  • Camila Gonzalo-Hansen
  • Marjolein van Sluis
  • Cindy M.A. Blom
  • Roel Janssens
  • Anja Raams
  • Dick Dekkers
  • Karel Bezstarosti
  • Dea Slade
6 more authors
  • Wim Vermeulen
  • Alex Pines
  • Jeroen A.A. Demmers
  • Carrie Bernecky
  • Titia Sixma
  • Jurgen Marteijn
Open at sourceDOICite

Abstract

Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4 CSA ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4 CSA serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment. However, the precise regulatory mechanisms of CRL4 CSA activity and TFIIH recruitment remain elusive. Here, we reveal human serine/threonine-protein kinase 19 (STK19) as a TC-NER factor, which is essential for correct DNA damage removal and subsequent transcription restart. Cryogenic electron microscopy (cryo-EM) studies demonstrate that STK19 is an integral part of the RNA Pol II-TC-NER complex, bridging CSA, UVSSA, RNA Pol II, and downstream DNA. STK19 stimulates TC-NER complex stability and CRL4 CSA activity, resulting in efficient RNA Pol II ubiquitylation and correct UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as a core TC-NER component.

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Cite

BibTeXRIS
BibTeX
@article{ramadhin2026stk19,
  title = {{STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment}},
  author = {Anisha Ramadhin and Shun-Hsiao Lee and Di Zhou and Anita Salmazo and Camila Gonzalo-Hansen and Marjolein van Sluis and Cindy M.A. Blom and Roel Janssens and Anja Raams and Dick Dekkers and Karel Bezstarosti and Dea Slade and Wim Vermeulen and Alex Pines and Jeroen A.A. Demmers and Carrie Bernecky and Titia Sixma and Jurgen Marteijn},
  journal = {Molecular Cell},
  year = {2026},
  month = oct,
  doi = {10.1016/j.molcel.2024.10.030},
  url = {https://hal.science/hal-05787642v1},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment
AU  - Anisha Ramadhin
AU  - Shun-Hsiao Lee
AU  - Di Zhou
AU  - Anita Salmazo
AU  - Camila Gonzalo-Hansen
AU  - Marjolein van Sluis
AU  - Cindy M.A. Blom
AU  - Roel Janssens
AU  - Anja Raams
AU  - Dick Dekkers
AU  - Karel Bezstarosti
AU  - Dea Slade
AU  - Wim Vermeulen
AU  - Alex Pines
AU  - Jeroen A.A. Demmers
AU  - Carrie Bernecky
AU  - Titia Sixma
AU  - Jurgen Marteijn
PY  - 2026
DA  - 2026/10/08
JO  - Molecular Cell
DO  - 10.1016/j.molcel.2024.10.030
UR  - https://hal.science/hal-05787642v1
AB  - Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4 CSA ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4 CSA serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment. However, the precise regulatory mechanisms of CRL4 CSA activity and TFIIH recruitment remain elusive. Here, we reveal human serine/threonine-protein kinase 19 (STK19) as a TC-NER factor, which is essential for correct DNA damage removal and subsequent transcription restart. Cryogenic electron microscopy (cryo-EM) studies demonstrate that STK19 is an integral part of the RNA Pol II-TC-NER complex, bridging CSA, UVSSA, RNA Pol II, and downstream DNA. STK19 stimulates TC-NER complex stability and CRL4 CSA activity, resulting in efficient RNA Pol II ubiquitylation and correct UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as a core TC-NER component.
SN  - 1097-2765
SN  - 1097-4164
ER  -