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TitleSTK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair.
Journal, issue, pagesCell, Vol. 187, Issue 25, Page 7107-7125.e25, Year 2024
Publish dateDec 12, 2024
AuthorsDiana van den Heuvel / Marta Rodríguez-Martínez / Paula J van der Meer / Nicolas Nieto Moreno / Jiyoung Park / Hyun-Suk Kim / Janne J M van Schie / Annelotte P Wondergem / Areetha D'Souza / George Yakoub / Anna E Herlihy / Krushanka Kashyap / Thierry Boissière / Jane Walker / Richard Mitter / Katja Apelt / Klaas de Lint / Idil Kirdök / Mats Ljungman / Rob M F Wolthuis / Patrick Cramer / Orlando D Schärer / Goran Kokic / Jesper Q Svejstrup / Martijn S Luijsterburg /
PubMed AbstractTranscription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, ...Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and transcription factor IIH (TFIIH) around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryoelectron microscopy (cryo-EM) and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.
External linksCell / PubMed:39547229 / PubMed Central
MethodsEM (single particle)
Resolution3.3 Å
Structure data

19909

9er2

EMDB-19909, PDB-9er2:
PolII-TCR-STK19 structure.
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-BEF:
BERYLLIUM TRIFLUORIDE ION

Source
  • homo sapiens (human)
  • sus scrofa (pig)
KeywordsTRANSCRIPTION / Complex / DNA repair

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