Back to Search Start Over

Structural basis of human transcription-DNA repair coupling.

Authors :
Kokic G
Wagner FR
Chernev A
Urlaub H
Cramer P
Source :
Nature [Nature] 2021 Oct; Vol. 598 (7880), pp. 368-372. Date of Electronic Publication: 2021 Sep 15.
Publication Year :
2021

Abstract

Transcription-coupled DNA repair removes bulky DNA lesions from the genome <superscript>1,2</superscript> and protects cells against ultraviolet (UV) irradiation <superscript>3</superscript> . 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 <superscript>CSA</superscript> and UV-stimulated scaffold protein A (UVSSA) <superscript>3</superscript> . 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 <superscript>3,4</superscript> 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 <superscript>TCR</superscript> , 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 <superscript>CSA</superscript> 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 <superscript>CSA</superscript> lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA.<br /> (© 2021. The Author(s).)

Details

Language :
English
ISSN :
1476-4687
Volume :
598
Issue :
7880
Database :
MEDLINE
Journal :
Nature
Publication Type :
Academic Journal
Accession number :
34526721
Full Text :
https://doi.org/10.1038/s41586-021-03906-4