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TitleSTK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment.
Journal, issue, pagesMol Cell, Vol. 84, Issue 24, Page 4740-4757.e12, Year 2024
Publish dateDec 19, 2024
AuthorsAnisha R Ramadhin / Shun-Hsiao Lee / Di Zhou / Anita Salmazo / Camila Gonzalo-Hansen / Marjolein van Sluis / Cindy M A Blom / Roel C Janssens / Anja Raams / Dick Dekkers / Karel Bezstarosti / Dea Slade / Wim Vermeulen / Alex Pines / Jeroen A A Demmers / Carrie Bernecky / Titia K Sixma / Jurgen A Marteijn /
PubMed AbstractTranscription-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 ...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 ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4 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 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 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.
External linksMol Cell / PubMed:39547223
MethodsEM (single particle)
Resolution3.0 - 4.2 Å
Structure data

EMDB-50292: Structure of Pol II-TC-NER-STK19 complex, consensus map
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-50293: Structure of Pol II-TC-NER-STK19 complex, focused on CSA-DDB1-DDA1-UVSSA-STK19
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-50294: Structure of Pol II-TC-NER-STK19 complex, focused on Pol II-ELOF1
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-50295: Structure of Pol II-TC-NER-STK19 complex, focused on CRL4CSA
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-50306: Structure of Pol II-TC-NER-STK19 complex, focused on CSA-DDB1-DDA1-CSB
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-50325: Structure of Pol II-TC-NER-STK19 complex, composite map
PDB-9fd2: Structure of Pol II-TC-NER-STK19 complex
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • sus scrofa domesticus (domestic pig)
KeywordsTRANSCRIPTION / Transcription-coupled DNA repair

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