Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation
Protein post-translational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signalling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Biochemistry and Molecular Biology
2018
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| _version_ | 1826276770217721856 |
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| author | Halim, VA García-Santisteban, I Warmerdam, DO van den Broek, B Heck, AJR Mohammed, S Medema, RH |
| author_facet | Halim, VA García-Santisteban, I Warmerdam, DO van den Broek, B Heck, AJR Mohammed, S Medema, RH |
| author_sort | Halim, VA |
| collection | OXFORD |
| description | Protein post-translational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signalling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell quantitative proteomics to identify global changes in protein ubiquitination that are induced by DNA double-strand breaks. In total, we quantified more than 9400 ubiquitin sites and found that the relative abundance of approximately 10% of these sites was altered in response to DNA double-strand breaks. Interestingly, a large proportion of ribosomal proteins, including those from the 40S as well as the 60S subunit, were ubiquitinated in response to DNA damage. In parallel, we discovered that DNA damage leads to the inhibition of ribosome function. Taken together, these data uncover the ribosome as a major target of the DNA damage response. |
| first_indexed | 2024-03-06T23:18:50Z |
| format | Journal article |
| id | oxford-uuid:680dfc9b-c4f2-4b97-b5a1-5bef9038b5be |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:18:50Z |
| publishDate | 2018 |
| publisher | American Society for Biochemistry and Molecular Biology |
| record_format | dspace |
| spelling | oxford-uuid:680dfc9b-c4f2-4b97-b5a1-5bef9038b5be2022-03-26T18:42:24ZDoxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:680dfc9b-c4f2-4b97-b5a1-5bef9038b5beEnglishSymplectic Elements at OxfordAmerican Society for Biochemistry and Molecular Biology2018Halim, VAGarcía-Santisteban, IWarmerdam, DOvan den Broek, BHeck, AJRMohammed, SMedema, RHProtein post-translational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signalling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell quantitative proteomics to identify global changes in protein ubiquitination that are induced by DNA double-strand breaks. In total, we quantified more than 9400 ubiquitin sites and found that the relative abundance of approximately 10% of these sites was altered in response to DNA double-strand breaks. Interestingly, a large proportion of ribosomal proteins, including those from the 40S as well as the 60S subunit, were ubiquitinated in response to DNA damage. In parallel, we discovered that DNA damage leads to the inhibition of ribosome function. Taken together, these data uncover the ribosome as a major target of the DNA damage response. |
| spellingShingle | Halim, VA García-Santisteban, I Warmerdam, DO van den Broek, B Heck, AJR Mohammed, S Medema, RH Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
| title | Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
| title_full | Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
| title_fullStr | Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
| title_full_unstemmed | Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
| title_short | Doxorubicin-induced DNA damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
| title_sort | doxorubicin induced dna damage causes extensive ubiquitination of ribosomal proteins associated with a decrease in protein translation |
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