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| Status |
Public on Dec 01, 2017 |
| Title |
Cockayne syndrome A and B proteins regulate the transcription arrest upon genotoxic stress through a ubiquitin/proteasome degradation process (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The rare genetic disease Cockayne syndrome (CS) results in mutations in CSA and CSB. Upon UV irradiation, RNA synthesis was arrested: RNA-seq showed 70% of down-regulated genes in common between CSA and CSB deficient cells. ATF3, the product of an immediate early gene was overexpressed and bound to its CRE/ATF site to inhibit its responsive genes. ChIP experiments showed that CSA/CUL4A/DDB1 together with CSB and MDM2, target ATF3. In vivo and in vitro experiments showed that ATF3 was ubiquitilated by a concerted action of CSA and MDM2 ubiquitin-ligases and was further eliminated by the proteasome concomitantly with the recruitment of RNA polymerase II to restart transcription. In CS cells, dysfunctional CSA or CSB were unable to assemble the ubiquitin/proteasome complex, thereby maintaining the ATF3-dependent transcription arrested. Though, in addition to their function in DNA repair, CSA and CSB might thus regulate the timing of DNA binding factors on its specific target site via the ubiquitin/proteasome machinery.
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| Overall design |
Examination kinetic of 8 samples including CS3BE, CSA, CS1AN, and CSB in 0, 8 and 24 hours, in wild type and CSB mutant cell lines.
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| |
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| Contributor(s) |
Epanchintsev A, Ye T, Egly J |
| Citation(s) |
29225035 |
| |
| Submission date |
Oct 02, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Tao YE |
| Organization name |
IGBMC (CNRS/INSERM/UDS)
|
| Street address |
1 rue Laurent Fries
|
| City |
Illkirch |
| ZIP/Postal code |
67404 |
| Country |
France |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE87564 |
Cockayne syndrome A and B proteins regulate the transcription arrest upon genotoxic stress through a ubiquitin/proteasome degradation process |
|
| Relations |
| BioProject |
PRJNA345197 |
| SRA |
SRP090755 |
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