期刊
MOLECULAR CELL
卷 68, 期 6, 页码 1054-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.11.009
关键词
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资金
- ERC [ERC2008-AdG-253077-Transreact]
- l'Agence Nationale de Recherche [ANpR-08MIEN-022-03, ANR-12-BSU8-0017-01, ANR-08-GENO-042-01]
- la Fondation ARC pour la Recherche contre le Cancer [ARC-PGA1*20160203862]
- l'Institut National du Cancer [INCA-2008-041]
- la Ligue contre le cancer (Equipe labelisee)
- AIRC [IG13074]
- Italian Telethon [GGP11176]
- ERC
- AFM
- French Ministere des Affaires Etrangeres
- Inserm Young investigator fellowship
- Marie Curie fellowship [FP7-PITN-GA-2012-316390]
- la Ligue contre le cancer
- French State fund [ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002-02]
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/pro-teasome machinery, regulates the recruitment timing of DNA-binding factors and provide explanations about the mechanism of transcription arrest following genotoxic stress.
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