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Doxorubicin-induced DNA Damage Causes Extensive Ubiquitination of Ribosomal Proteins Associated with a Decrease in Protein Translation

Halim, V. A., Garcia-Santisteban, I., Warmerdam, D. O., van den Broek, W., Heck, A. J. R., Mohammed, S. & Medema, R. H., Dec-2018, In : Molecular & Cellular Proteomics. 17, 12, p. 2297-2308 12 p., UNSP RA118.000652.

Research output: Contribution to journalArticleAcademicpeer-review

  • Vincentius A. Halim
  • Iraia Garcia-Santisteban
  • Daniel O. Warmerdam
  • WaBram van den Broek
  • Albert J. R. Heck
  • Shabaz Mohammed
  • Rene H. Medema

Protein posttranslational 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 signaling 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 9,400 ubiquitin sites and found that the relative abundance of similar to 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.

Original languageEnglish
Article numberUNSP RA118.000652
Pages (from-to)2297-2308
Number of pages12
JournalMolecular & Cellular Proteomics
Volume17
Issue number12
Publication statusPublished - Dec-2018

    Keywords

  • POLO-LIKE KINASE-1, MESSENGER-RNAS, P53, RECOVERY, REPAIR, UBIQUITYLATION, IDENTIFICATION, RECRUITMENT, CLASPIN, QUANTIFICATION

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