SNAP output for PDB entry 7opc [SNAP web server]

PDB-id

7opc; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription

Method

cryo-EM (3.0 Å)

Summary

Pol ii-csb-crl4csa-uvssa-spt6-paf (structure 4)

Reference

Kokic G, Wagner FR, Chernev A, Urlaub H, Cramer P (2021): "Structural basis of human transcription-DNA repair coupling." Nature, 598, 368-372. doi: 10.1038/s41586-021-03906-4.

Abstract

Transcription-coupled DNA repair removes bulky DNA lesions from the genome_1,2 and protects cells against ultraviolet (UV) irradiation₃. 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_CSA and UV-stimulated scaffold protein A (UVSSA)₃. 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_3,4 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_TCR, 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_CSA 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_CSA lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA.