Author
Listed:
- Estefanie Dufey
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- José Manuel Bravo-San Pedro
(Université de Paris, Sorbonne Université
Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus)
- Cristian Eggers
(University of Chile
University of Chile)
- Matías González-Quiroz
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile
Proteostasis & Cancer Team, INSERM U1242, University of Rennes 1)
- Hery Urra
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- Alfredo I. Sagredo
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- Denisse Sepulveda
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- Philippe Pihán
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- Amado Carreras-Sureda
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- Younis Hazari
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile)
- Eduardo A. Sagredo
(Stockholm University, Svante Arrheniusväg 20C)
- Daniela Gutierrez
(Pontificia Universidad Católica de Chile)
- Cristian Valls
(Pontificia Universidad Católica de Chile)
- Alexandra Papaioannou
(Proteostasis & Cancer Team, INSERM U1242, University of Rennes 1
Centre de Lutte contre le Cancer Eugène Marquis)
- Diego Acosta-Alvear
(University of California
University of California, San Francisco
University of California, Santa Barbara)
- Gisela Campos
(IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund)
- Pedro M. Domingos
(Universidade Nova de Lisboa, Av. da República)
- Rémy Pedeux
(Proteostasis & Cancer Team, INSERM U1242, University of Rennes 1
Centre de Lutte contre le Cancer Eugène Marquis)
- Eric Chevet
(Proteostasis & Cancer Team, INSERM U1242, University of Rennes 1
Centre de Lutte contre le Cancer Eugène Marquis)
- Alejandra Alvarez
(Pontificia Universidad Católica de Chile)
- Patricio Godoy
(IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund)
- Peter Walter
(University of California
University of California, San Francisco)
- Alvaro Glavic
(University of Chile
University of Chile)
- Guido Kroemer
(Université de Paris, Sorbonne Université
Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus
Hôpital Européen Georges Pompidou, AP-HP
Chinese Academy of Medical Sciences)
- Claudio Hetz
(University of Chile
Brain Health and Metabolism (GERO)
University of Chile
The Buck Institute for Research in Aging)
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.
Suggested Citation
Estefanie Dufey & José Manuel Bravo-San Pedro & Cristian Eggers & Matías González-Quiroz & Hery Urra & Alfredo I. Sagredo & Denisse Sepulveda & Philippe Pihán & Amado Carreras-Sureda & Younis Hazari &, 2020.
"Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response,"
Nature Communications, Nature, vol. 11(1), pages 1-13, December.
Handle:
RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15694-y
DOI: 10.1038/s41467-020-15694-y
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