A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner
| العنوان: | A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner |
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| المؤلفون: | Sandrine Ragu, Nathalie Droin, Gabriel Matos-Rodrigues, Aurélia Barascu, Sylvain Caillat, Gabriella Zarkovic, Capucine Siberchicot, Elodie Dardillac, Camille Gelot, Josée Guirouilh-Barbat, J. Pablo Radicella, Alexander A. Ishchenko, Jean-Luc Ravanat, Eric Solary, Bernard S. Lopez |
| المساهمون: | Commissariat à l'Energie Atomique, Institut de Radiobiologie Cellulaire et Moléculaire (CEA, IBFJ, IRCM) |
| المصدر: | Cell Death and Differentiation Cell Death and Differentiation, 2023, 30 (5), pp.1349-1365. ⟨10.1038/s41418-023-01141-0⟩ |
| بيانات النشر: | HAL CCSD, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio], Cell Biology, Molecular Biology |
| الوصف: | Cells are inevitably challenged by low-level/endogenous stresses that do not arrest DNA replication. Here, in human primary cells, we discovered and characterized a noncanonical cellular response that is specific to nonblocking replication stress. Although this response generates reactive oxygen species (ROS), it induces a program that prevents the accumulation of premutagenic 8-oxoguanine in an adaptive way. Indeed, replication stress-induced ROS (RIR) activate FOXO1-controlled detoxification genes such as SEPP1, catalase, GPX1, and SOD2. Primary cells tightly control the production of RIR: They are excluded from the nucleus and are produced by the cellular NADPH oxidases DUOX1/DUOX2, whose expression is controlled by NF-κB, which is activated by PARP1 upon replication stress. In parallel, inflammatory cytokine gene expression is induced through the NF-κB-PARP1 axis upon nonblocking replication stress. Increasing replication stress intensity accumulates DNA double-strand breaks and triggers the suppression of RIR by p53 and ATM. These data underline the fine-tuning of the cellular response to stress that protects genome stability maintenance, showing that primary cells adapt their responses to replication stress severity. |
| اللغة: | English |
| تدمد: | 1350-9047 1476-5403 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b20cee5f73d5b182d62f8ba591e51bc https://cea.hal.science/cea-04157573 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7b20cee5f73d5b182d62f8ba591e51bc |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 13509047 14765403 |
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