Large scale ubiquitination in doxorubicin treated cells

Protein post-translational modification (PTM) plays a central role in the DNA damage response. In particular protein phosphorylation and ubiquitination have been shown to play a major role in the signalling cascade that coordinates break repair with cell cycle progression. Here we performed large-scale quantitative proteomics to identify changes in protein ubiquitination that are induced by DNA double-strand breaks. In total we quantified >9400 ubiquitin sites, and found that the relative abundance of ~10% of these sites was altered in response to DNA double-strand breaks. Interestingly, we found a large proportion of the ribosomal proteins to be ubiquitinated after damage. These included ribosomal proteins from the 40S as well as the 60S subunit. We subsequently show that DNA damage damage leads to a transient inhibition in ribosome function in protein synthesis. Taken together, these data uncover ribosome ubiquitination as a consequence of activation of the DDR .