TRiC controls transcription resumption after UV damage by regulating Cockayne syndrome protein A

Nat Commun. 2018 Mar 12;9(1):1040. doi: 10.1038/s41467-018-03484-6.


Transcription-blocking DNA lesions are removed by transcription-coupled nucleotide excision repair (TC-NER) to preserve cell viability. TC-NER is triggered by the stalling of RNA polymerase II at DNA lesions, leading to the recruitment of TC-NER-specific factors such as the CSA-DDB1-CUL4A-RBX1 cullin-RING ubiquitin ligase complex (CRLCSA). Despite its vital role in TC-NER, little is known about the regulation of the CRLCSA complex during TC-NER. Using conventional and cross-linking immunoprecipitations coupled to mass spectrometry, we uncover a stable interaction between CSA and the TRiC chaperonin. TRiC's binding to CSA ensures its stability and DDB1-dependent assembly into the CRLCSA complex. Consequently, loss of TRiC leads to mislocalization and depletion of CSA, as well as impaired transcription recovery following UV damage, suggesting defects in TC-NER. Furthermore, Cockayne syndrome (CS)-causing mutations in CSA lead to increased TRiC binding and a failure to compose the CRLCSA complex. Thus, we uncover CSA as a TRiC substrate and reveal that TRiC regulates CSA-dependent TC-NER and the development of CS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Chaperonin Containing TCP-1 / genetics
  • Chaperonin Containing TCP-1 / metabolism*
  • Cockayne Syndrome / genetics
  • DNA Damage / genetics
  • DNA Damage / radiation effects*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Microscopy, Fluorescence
  • Mutation / genetics
  • RNA Interference
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics
  • Transcription, Genetic / radiation effects
  • Ultraviolet Rays*


  • ERCC8 protein, human
  • Transcription Factors
  • Chaperonin Containing TCP-1
  • DNA Repair Enzymes