Double stranded DNA breaks and genome editing trigger loss of ribosomal protein RPS27A
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Date
2022-06
Publication Type
Journal Article
ETH Bibliography
yes
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Abstract
DNA damage activates a robust transcriptional stress response, but much less is known about how DNA damage impacts translation. The advent of genome editing with Cas9 has intensified interest in understanding cellular responses to DNA damage. Here, we find that DNA double-strand breaks (DSBs), including those induced by Cas9, trigger the loss of ribosomal protein RPS27A from ribosomes via p53-independent proteasomal degradation. Comparisons of Cas9 and dCas9 ribosome profiling and mRNA-seq experiments reveal a global translational response to DSBs that precedes changes in transcript abundance. Our results demonstrate that even a single DSB can lead to altered translational output and ribosome remodeling, suggesting caution in interpreting cellular phenotypes measured immediately after genome editing.
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Publication status
published
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Book title
Journal / series
Volume
289 (11)
Pages / Article No.
3101 - 3114
Publisher
Wiley-Blackwell
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Edition / version
Methods
Software
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Date collected
Date created
Subject
DNA damage response; genome editing; ribosomes; translation
Organisational unit
09635 - Corn, Jacob / Corn, Jacob
09635 - Corn, Jacob / Corn, Jacob
02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences