9BZ0

Structure of an STK19-containing TC-NER complex

Summary for 9BZ0

• Entry DOI: 10.2210/pdb9bz0/pdb
• EMDB information: 45050
• Descriptor: DNA-directed RNA polymerase subunit, DNA-directed RNA polymerases I, II, and III subunit RPABC5, RNA polymerase II subunit J, ... (25 entities in total)
• Functional Keywords: dna repair, rna polymerase ii, co-transcriptional process, transcription, transcription-dna-rna complex, transcription/dna/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 22
• Total formula weight: 1058103.88

Authors

Mevissen, T.E.T.,Kuemmecke, M.,Farnung, L.,Walter, J.C. (deposition date: 2024-05-24, release date: 2024-12-25, Last modification date: 2025-01-15)

Primary citation

Mevissen, T.E.T.,Kummecke, M.,Schmid, E.W.,Farnung, L.,Walter, J.C.
STK19 positions TFIIH for cell-free transcription-coupled DNA repair.
Cell, 187:7091-7106.e24, 2024

PubMed Abstract: In transcription-coupled nucleotide excision repair (TC-NER), stalled RNA polymerase II (RNA Pol II) binds CSB and CRL4, which cooperate with UVSSA and ELOF1 to recruit TFIIH. To explore the mechanism of TC-NER, we recapitulated this reaction in vitro. When a plasmid containing a site-specific lesion is transcribed in frog egg extract, error-free repair is observed that depends on CSB, CRL4, UVSSA, and ELOF1. Repair also requires STK19, a factor previously implicated in transcription recovery after UV exposure. A 1.9-Å cryo-electron microscopy structure shows that STK19 binds the TC-NER complex through CSA and the RPB1 subunit of RNA Pol II. Furthermore, AlphaFold predicts that STK19 interacts with the XPD subunit of TFIIH, and disrupting this interface impairs cell-free repair. Molecular modeling suggests that STK19 positions TFIIH ahead of RNA Pol II for lesion verification. Our analysis of cell-free TC-NER suggests that STK19 couples RNA Pol II stalling to downstream repair events.

PubMed: 39547228
DOI: 10.1016/j.cell.2024.10.020

Experimental method

ELECTRON MICROSCOPY (1.9 Å)