| First Author | Dufey E | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2401 |
| PubMed ID | 32409639 | Mgi Jnum | J:293066 |
| Mgi Id | MGI:6447278 | Doi | 10.1038/s41467-020-15694-y |
| Citation | Dufey E, et al. (2020) Genotoxic stress triggers the activation of IRE1alpha-dependent RNA decay to modulate the DNA damage response. Nat Commun 11(1):2401 |
| abstractText | The molecular connections between homeostatic systems that maintain both genome integrity and proteostasis are poorly understood. Here we identify the selective activation of the unfolded protein response transducer IRE1alpha under genotoxic stress to modulate repair programs and sustain cell survival. DNA damage engages IRE1alpha signaling in the absence of an endoplasmic reticulum (ER) stress signature, leading to the exclusive activation of regulated IRE1alpha-dependent decay (RIDD) without activating its canonical output mediated by the transcription factor XBP1. IRE1alpha endoribonuclease activity controls the stability of mRNAs involved in the DNA damage response, impacting DNA repair, cell cycle arrest and apoptosis. The activation of the c-Abl kinase by DNA damage triggers the oligomerization of IRE1alpha to catalyze RIDD. The protective role of IRE1alpha under genotoxic stress is conserved in fly and mouse. Altogether, our results uncover an important intersection between the molecular pathways that sustain genome stability and proteostasis. |
