AI Article Synopsis
- UV radiation can harm both DNA and RNA in cells, causing different stress responses when cells are damaged.
- Researchers studied how cells react to UV damage using various scientific methods to understand the timing and effects of these responses.
- They found that a specific protein called ZAK controls cell death after UV damage and is regulated by two different feedback systems to help maintain balance in the cells.
Article Abstract
While ultraviolet (UV) radiation damages DNA, eliciting the DNA damage response (DDR), it also damages RNA, triggering transcriptome-wide ribosomal collisions and eliciting a ribotoxic stress response (RSR). However, the relative contributions, timing, and regulation of these pathways in determining cell fate is unclear. Here we use time-resolved phosphoproteomic, chemical-genetic, single-cell imaging, and biochemical approaches to create a chronological atlas of signaling events activated in cells responding to UV damage. We discover that UV-induced apoptosis is mediated by the RSR kinase ZAK and not through the DDR. We identify two negative-feedback modules that regulate ZAK-mediated apoptosis: (1) GCN2 activation limits ribosomal collisions and attenuates ZAK-mediated RSR and (2) ZAK activity leads to phosphodegron autophosphorylation and its subsequent degradation. These events tune ZAK's activity to collision levels to establish regimes of homeostasis, tolerance, and death, revealing its key role as the cellular sentinel for nucleic acid damage.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246228 | PMC |
| http://dx.doi.org/10.1016/j.cell.2024.05.018 | DOI Listing |
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