6FCV

Structure of the human DDB1-CSA complex

Summary for 6FCV

• Entry DOI: 10.2210/pdb6fcv/pdb
• Related: 4A11
• Descriptor: DNA damage-binding protein 1, DNA excision repair protein ERCC-8 (2 entities in total)
• Functional Keywords: dna damage response protein, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 175695.63

Authors

Meulenbroek, E.M.,Pannu, N.S. (deposition date: 2017-12-21, release date: 2019-01-30, Last modification date: 2024-01-17)

Primary citation

Pines, A.,Dijk, M.,Makowski, M.,Meulenbroek, E.M.,Vrouwe, M.G.,van der Weegen, Y.,Baltissen, M.,French, P.J.,van Royen, M.E.,Luijsterburg, M.S.,Mullenders, L.H.,Vermeulen, M.,Vermeulen, W.,Pannu, N.S.,van Attikum, H.
TRiC controls transcription resumption after UV damage by regulating Cockayne syndrome protein A.
Nat Commun, 9:1040-1040, 2018

PubMed Abstract: 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 (CRL). Despite its vital role in TC-NER, little is known about the regulation of the CRL 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 CRL 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 CRL complex. Thus, we uncover CSA as a TRiC substrate and reveal that TRiC regulates CSA-dependent TC-NER and the development of CS.

PubMed: 29531219
DOI: 10.1038/s41467-018-03484-6

Experimental method

X-RAY DIFFRACTION (2.92 Å)