A link between DNA double-strand breaks and regulation of global translation.

In response to double-strand breaks (DSBs) in the DNA, cells undergo transcriptional, translational and post-translational reprogramming to tackle the damage. In this study by Riepe et al., the authors have shown that the global translation inhibition of proteins is concomitant to DNA damage response. Treatment with various DSB-generating agents can cause a major downregulation in the translation of cellular proteins except for the ISR (integrated stress response) proteins. Authors report a specific and significant reduction in the level of a core ribosomal RPS27A protein coupled to kinetics of DSB induction and repair. The study proposes that molecular alterations generated as a by-product of DNA damage may inadvertently impact phenotypic responses of the cells and a cautious approach must be followed when utilizing DSB-based genome editing techniques. Comment on: https://doi.org/10.1111/febs.16321.