ArticleCell death and differentiation2023
A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Pamiparib as consolidation treatment after concurrent chemoradiotherapy of limited-stage small cell lung cancer: a single-arm, open-label phase 2 trial.Radiation oncology (London, England) · 2024Trial
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Zn-Quer Nanozymes Reprogram the Malignant Phenotypic Transformation of Gastric Cancer Cells via Cascade Reactive Oxygen Species Coordination.ACS applied materials & interfaces · 2026Article
- Molecular Regulation of FOXO1 and Its Pathophysiological Significance in Endometriosis: A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- Review
- Dysregulation of the low-level replication stress response in transformed cell lines.Scientific reports · 2025Article
- Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death.Nature communications · 2025Article
- Oxidative replication stress induced by long-term exposure to hydroxyurea in root meristem cells of Vicia faba.Plant cell reports · 2024Article
- FoxO1-Overexpressed Small Extracellular Vesicles Derived from hPDLSCs Promote Periodontal Tissue Regeneration by Reducing Mitochondrial Dysfunction to Regulate Osteogenesis and Inflammation.International journal of nanomedicine · 2024Article
- Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023Review
- In vivo reduction of RAD51-mediated homologous recombination triggers aging but impairs oncogenesis.The EMBO journal · 2023Article
- Simulating Space Conditions Evokes Different DNA Damage Responses in Immature and Mature Cells of the Human Hematopoietic System.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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