UV radiation not only induces DNA damage, but also damages RNA, eliciting a ribotoxic stress response (RSR), but its contribution to subsequent cell death remains unclear. Green and colleagues establish a detailed timeline of signalling events activated in cells upon UV damage and report that UV-mediated apoptosis is driven by RSR, and not the DNA damage response.

The authors show that the immediate-early UV radiation response is dominated by ribosome-mediated signalling with activation of the RSR kinases ZAK and GCN2, and subsequent cell death; this is driven by RSR as inhibition of ZAK, but not of the DNA damage response, prior to radiating cells prevents apoptosis. They then explore the role of GCN2 and find that its activation limits ribosomal collisions, attenuating ZAK and resolving ribotoxic stress. Furthermore, ZAK activation results in its autophosphorylation and subsequent degradation, which, in turn, restricts apoptosis to enable tolerance under persistent ribotoxic stress.

紫外线辐射不仅会引起 DNA 损伤，还会损伤 RNA，引发核糖毒性应激反应 (RSR)，但其对随后细胞死亡的影响仍不清楚。 Green 及其同事建立了紫外线损伤后细胞中激活的信号事件的详细时间表，并报告说紫外线介导的细胞凋亡是由 RSR 驱动的，而不是 DNA 损伤反应。

作者表明，立即早期的紫外线辐射反应主要是核糖体介导的信号传导，激活 RSR 激酶 ZAK 和 GCN2，以及随后的细胞死亡；这是由 RSR 驱动的，因为在辐射细胞之前抑制 ZAK，但不抑制 DNA 损伤反应，从而防止细胞凋亡。然后，他们探索了 GCN2 的作用，发现它的激活限制了核糖体碰撞，减弱了 ZAK 并解决了核糖毒性应激。此外，ZAK 激活会导致其自身磷酸化和随后的降解，从而限制细胞凋亡，从而在持续的核糖毒性应激下实现耐受。