Double stranded DNA breaks and genome editing trigger loss of ribosomal protein RPS27A.
Double stranded DNA breaks and genome editing trigger loss of ribosomal protein RPS27A.
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DOI：
10.1111/febs.16321
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发表时间：
2022-06
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影响因子：
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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. DNA damage activates a robust transcriptional stress response; however, how DNA damage impacts translation remains understudied. The emergence of Cas9‐based genome editing has intensified interest in elucidating cellular responses to DNA damage. Here, Nicholas Ingolia, Jacob Corn and colleagues describe how DNA double‐strand breaks (DSBs), including Cas9‐induced DSBs, trigger loss of ribosomal protein RPS27A from ribosomes. Comparison between Cas9 and dCas9 ribosome profiling and mRNA‐seq experiments reveal a translational response to DSBs that precedes transcriptional changes. The authors show that Cas9‐associated DSBs can cause altered translation and ribosome remodelling, suggesting caution in interpreting cellular phenotypes measured immediately after genome editing.
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影响因子：
2.5
作者：
Schindelin J;Rueden CT;Hiner MC;Eliceiri KW
通讯作者：
Eliceiri KW
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通讯作者：
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影响因子：
14.8
作者：
Ingolia, Nicholas T.;Brar, Gloria A.;Rouskin, Silvia;McGeachy, Anna M.;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.