ArticleBMC biology2020
Persistent DNA damage triggers activation of the integrated stress response to promote cell survival under nutrient restriction.
Article in BMC biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
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- Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death inHemaSphere · 2026Article
- Oocyte-specific knockout of eIF2 subunits causes apoptosis of mouse oocytes within the early growing follicles via mitochondrial dysfunctions and DNA damage.Cell death & disease · 2026Article
- Molecular pathways linking chronic psychological stress to accelerated aging: mechanisms and interventions.Frontiers in aging · 2026Review
- Evaluation ofCancer management and research · 2026Article
- The Prognostic Value of the XPC rs2228001 Single Nucleotide Polymorphism in Cholangiocarcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- A Case-Control Study on Combined Effects of Base Excision Repair and Nucleotide Excision Repair Gene Polymorphisms in Gastrointestinal Cancer Susceptibility.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Diverse roles of stress-responsive RNP granules in oogenesis and infertility.Biology of reproduction · 2025Review
- Role of MRE11 in DNA damage repair pathway dynamics and its diagnostic and prognostic significance in hereditary breast and ovarian cancer.BMC cancer · 2025Article
- Spatio-temporal transcriptomic analysis reveals distinct nephrotoxicity, DNA damage, and regeneration response after cisplatin.Cell biology and toxicology · 2025Article
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Premeiotic deletion of Eif2s2 causes oocyte arrest at the early diplotene stage and apoptosis in mice.Cell proliferation · 2024Article
- Role of Oxidative Stress in Blood-Brain Barrier Disruption and Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Inhibition ofeLife · 2024Article
- Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics.Oncotarget · 2024Article
- Impact of tRNA-induced proline-to-serine mistranslation on the transcriptome of Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Exercise to Mitigate Cerebrovascular Aging: A Geroscience Perspective.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Review
- Inhibition ofbioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBase-excision repair (BER) is a central DNA repair mechanism responsible for the maintenance of genome integrity. Accordingly, BER defects have been implicated in cancer, presumably by precipitating cellular transformation through an increase in the occurrence of mutations. Hence, tight adaptation of BER capacity is essential for DNA stability. However, counterintuitive to this, prolonged exposure of cells to pro-inflammatory molecules or DNA-damaging agents causes a BER deficiency by downregulating the central scaffold protein XRCC1. The rationale for this XRCC1 downregulation in response to persistent DNA damage remains enigmatic. Based on our previous findings that XRCC1 downregulation causes wide-ranging anabolic changes, we hypothesised that BER depletion could enhance cellular survival under stress, such as nutrient restriction.
resultsHere, we demonstrate that persistent single-strand breaks (SSBs) caused by XRCC1 downregulation trigger the integrated stress response (ISR) to promote cellular survival under nutrient-restricted conditions. ISR activation depends on DNA damage signalling via ATM, which triggers PERK-mediated eIF2α phosphorylation, increasing translation of the stress-response factor ATF4. Furthermore, we demonstrate that SSBs, induced either through depletion of the transcription factor Sp1, responsible for XRCC1 levels, or through prolonged oxidative stress, trigger ISR-mediated cell survival under nutrient restriction as well. Finally, the ISR pathway can also be initiated by persistent DNA double-strand breaks.
conclusionsOur results uncover a previously unappreciated connection between persistent DNA damage, caused by a decrease in BER capacity or direct induction of DNA damage, and the ISR pathway that supports cell survival in response to genotoxic stress with implications for tumour biology and beyond.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.