| Autor: |
Elena Zelin, Nicholas T. Ingolia, Alexander Marson, Jr Liang, Jonathan T. Vu, Jacob E. Corn, C Riepe, Stacia K. Wyman, Phillip A. Frankino, David N. Nguyen, Zuriah A. Meacham |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| DOI: |
10.1101/486704 |
| Popis: |
SummaryDNA damage activates a robust transcriptional stress response, but much less is known about how DNA impacts translation. The advent of genome editing via a Cas9-induced DNA double-strand break has intensified interest in understanding cellular responses to DNA damage. Here we find that DNA double-strand breaks (DSBs) induced by Cas9 or other damaging agents lead to a reduction of core ribosomal proteins, RPS27A and RPL40, and that the loss of these proteins is post-transcriptional and p53-independent. DSBs furthermore lead to the shutdown of translation through phosphorylation of eukaryotic initiation factor 2 alpha, and altering these signals affects genome editing outcomes. This DSB translational response is widespread and precedes the transcriptional response. Our results demonstrate that even a single double-strand break can lead to ribosome remodeling and reduced translational output, and suggest caution in interpreting cellular phenotypes measured immediately after genome editing. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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