9FD2

Structure of Pol II-TC-NER-STK19 complex

Summary for 9FD2

• Entry DOI: 10.2210/pdb9fd2/pdb
• EMDB information: 50325
• Descriptor: DNA-directed RNA polymerase subunit, DNA-directed RNA polymerases I, II, and III subunit RPABC5, DNA-directed RNA polymerase II subunit RPB11-a, ... (24 entities in total)
• Functional Keywords: transcription-coupled dna repair, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 22
• Total formula weight: 1058537.68

Authors

Lee, S.-H.,Sixma, T.K. (deposition date: 2024-05-16, release date: 2024-11-13, Last modification date: 2024-11-27)

Primary citation

Ramadhin, A.R.,Lee, S.H.,Zhou, D.,Salmazo, A.,Gonzalo-Hansen, C.,van Sluis, M.,Blom, C.M.A.,Janssens, R.C.,Raams, A.,Dekkers, D.,Bezstarosti, K.,Slade, D.,Vermeulen, W.,Pines, A.,Demmers, J.A.A.,Bernecky, C.,Sixma, T.K.,Marteijn, J.A.
STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment.
Mol.Cell, 2024

PubMed 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 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.

PubMed: 39547223
DOI: 10.1016/j.molcel.2024.10.030

Experimental method

ELECTRON MICROSCOPY (3.4 Å)