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

Simple item page
dc.contributor.authorDufey, Estefanie
dc.contributor.authorBravo-San Pedro, Jose Manuel
dc.contributor.authorEggers, Cristian
dc.contributor.authorGonzalez-Quiroz, Matias
dc.contributor.authorUrra, Hery
dc.contributor.authorSagredo, Alfredo, I
dc.contributor.authorSepulveda, Denisse
dc.contributor.authorPihan, Philippe
dc.contributor.authorCarreras-Sureda, Amado
dc.contributor.authorHazari, Younis
dc.contributor.authorSagredo, Eduardo A.
dc.contributor.authorGutierrez, Daniela
dc.contributor.authorValls, Cristian
dc.contributor.authorPapaioannou, Alexandra
dc.contributor.authorAcosta-Alvear, Diego
dc.contributor.authorCampos, Gisela
dc.contributor.authorDomingos, Pedro M.
dc.contributor.authorPedeux, Remy
dc.contributor.authorChevet, Eric
dc.contributor.authorAlvarez, Alejandra
dc.contributor.authorGodoy, Patricio
dc.contributor.authorWalter, Peter
dc.contributor.authorGlavic, Alvaro
dc.contributor.authorKroemer, Guido
dc.contributor.authorHetz, Claudio
dc.date.accessioned2025-01-23T19:52:05Z
dc.date.available2025-01-23T19:52:05Z
dc.date.issued2020
dc.description.abstractThe 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 IRE1 alpha under genotoxic stress to modulate repair programs and sustain cell survival. DNA damage engages IRE1 alpha signaling in the absence of an endoplasmic reticulum (ER) stress signature, leading to the exclusive activation of regulated IRE1 alpha -dependent decay (RIDD) without activating its canonical output mediated by the transcription factor XBP1. IRE1 alpha 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 IRE1 alpha to catalyze RIDD. The protective role of IRE1 alpha 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. IRE1 alpha plays a key role in the unfolded protein response (UPR) by promoting the unconventional splicing of the XBP1 and the selective cleavage of RNAs. Here the authors report that IRE1 alpha is activated upon the DNA damage response and selectively controls the stability of mRNAs to maintain genome integrity.
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41467-020-15694-y
dc.identifier.issn2041-1723
dc.identifier.urihttps://doi.org/10.1038/s41467-020-15694-y
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100616
dc.identifier.wosidWOS:000558691000001
dc.issue.numero1
dc.language.isoen
dc.revistaNature communications
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGenotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response
dc.typeartículo
dc.volumen11
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas