Fiche publication
Date publication
décembre 2017
Journal
Molecular cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COIN Frédéric
,
Dr EGLY Jean-Marc
Tous les auteurs :
Epanchintsev A, Costanzo F, Rauschendorf MA, Caputo M, Ye T, Donnio LM, Proietti-de-Santis L, Coin F, Laugel V, Egly JM
Lien Pubmed
Résumé
Cockayne syndrome (CS) is caused by mutations in CSA and CSB. The CSA and CSB proteins have been linked to both promoting transcription-coupled repair and restoring transcription following DNA damage. We show that UV stress arrests transcription of approximately 70% of genes in CSA- or CSB-deficient cells due to the constitutive presence of ATF3 at CRE/ATF sites. We found that CSB, CSA/DDB1/CUL4A, and MDM2 were essential for ATF3 ubiquitination and degradation by the proteasome. ATF3 removal was concomitant with the recruitment of RNA polymerase II and the restart of transcription. Preventing ATF3 ubiquitination by mutating target lysines prevented recovery of transcription and increased cell death following UV treatment. Our data suggest that the coordinate action of CSA and CSB, as part of the ubiquitin/proteasome machinery, regulates the recruitment timing of DNA-binding factors and provide explanations about the mechanism of transcription arrest following genotoxic stress.
Mots clés
ATF3, CSA, CSB, DNA repair, MDM2, TCR, proteasome, transcription, transcription arrest, ubiquitination
Référence
Mol. Cell. 2017 Dec 21;68(6):1054-1066.e6
