Skip to Main content Skip to Navigation
Journal articles

Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response

Abstract : 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 IRE1α under genotoxic stress to modulate repair programs and sustain cell survival. DNA damage engages IRE1α signaling in the absence of an endoplasmic reticulum (ER) stress signature, leading to the exclusive activation of regulated IRE1α-dependent decay (RIDD) without activating its canonical output mediated by the transcription factor XBP1. IRE1α 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 IRE1α to catalyze RIDD. The protective role of IRE1α 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.
Document type :
Journal articles
Complete list of metadatas

https://hal-univ-rennes1.archives-ouvertes.fr/hal-02862260
Contributor : Laurent Jonchère <>
Submitted on : Tuesday, June 9, 2020 - 1:43:44 PM
Last modification on : Tuesday, July 21, 2020 - 3:50:20 AM

File

qt4789w8jr.pdf?t=qaxr0i
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Estefanie Dufey, José Manuel Bravo-San Pedro, Cristian Eggers, Matías González-Quiroz, Hery Urra, et al.. Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.2401. ⟨10.1038/s41467-020-15694-y⟩. ⟨hal-02862260⟩

Share

Metrics

Record views

23

Files downloads

36