7OO3

Pol II-CSB-CSA-DDB1-UVSSA (Structure1)

Summary for 7OO3

• Entry DOI: 10.2210/pdb7oo3/pdb
• EMDB information: 13004
• Descriptor: DNA-directed RNA polymerase II subunit RPB1, DNA-directed RNA polymerases I, II, and III subunit RPABC5, RNA_pol_L_2 domain-containing protein, ... (22 entities in total)
• Functional Keywords: transcription, dna repair
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 20
• Total formula weight: 973828.42

Authors

Kokic, G.,Cramer, P. (deposition date: 2021-05-26, release date: 2021-10-06, Last modification date: 2024-07-10)

Primary citation

Kokic, G.,Wagner, F.R.,Chernev, A.,Urlaub, H.,Cramer, P.
Structural basis of human transcription-DNA repair coupling.
Nature, 598:368-372, 2021

PubMed Abstract: Transcription-coupled DNA repair removes bulky DNA lesions from the genome and protects cells against ultraviolet (UV) irradiation. Transcription-coupled DNA repair begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CSB, the E3 ubiquitin ligase, CRL4 and UV-stimulated scaffold protein A (UVSSA). Here we provide five high-resolution structures of Pol II transcription complexes containing human transcription-coupled DNA repair factors and the elongation factors PAF1 complex (PAF) and SPT6. Together with biochemical and published data, the structures provide a model for transcription-repair coupling. Stalling of Pol II at a DNA lesion triggers replacement of the elongation factor DSIF by CSB, which binds to PAF and moves upstream DNA to SPT6. The resulting elongation complex, EC, uses the CSA-stimulated translocase activity of CSB to pull on upstream DNA and push Pol II forward. If the lesion cannot be bypassed, CRL4 spans over the Pol II clamp and ubiquitylates the RPB1 residue K1268, enabling recruitment of TFIIH to UVSSA and DNA repair. Conformational changes in CRL4 lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA.

PubMed: 34526721
DOI: 10.1038/s41586-021-03906-4

Experimental method

ELECTRON MICROSCOPY (2.8 Å)