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

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 culli...

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Detalles Bibliográficos
Autores principales: Pines, Alex, Dijk, Madelon, Makowski, Matthew, Meulenbroek, Elisabeth M., Vrouwe, Mischa G., van der Weegen, Yana, Baltissen, Marijke, French, Pim J., van Royen, Martin E., Luijsterburg, Martijn S., Mullenders, Leon H., Vermeulen, Michiel, Vermeulen, Wim, Pannu, Navraj S., van Attikum, Haico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847541/
https://www.ncbi.nlm.nih.gov/pubmed/29531219
http://dx.doi.org/10.1038/s41467-018-03484-6
Descripción
Sumario: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(CSA)). Despite its vital role in TC-NER, little is known about the regulation of the CRL(CSA) 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(CSA) 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(CSA) complex. Thus, we uncover CSA as a TRiC substrate and reveal that TRiC regulates CSA-dependent TC-NER and the development of CS.