ArticleNature communications2021
Hypoxia-induced SETX links replication stress with the unfolded protein response.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review.Biochemical Society transactions · 2021Pooled it
- Article
- Review
- Wild-typemedRxiv : the preprint server for health sciences · 2026Article
- Hypoxic glycolysis-driven histone lactylation activates NHE7 to promote endometrial cancer progression via COX6C-mediated endoplasmic reticulum stress.Apoptosis : an international journal on programmed cell death · 2026Article
- Senataxin regulates cisplatin resistance through an R-loop-mediated mechanism in HPV-associated head and neck cancer.iScience · 2025Article
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- Dual inhibition of DNA damage repair sensitizes photodynamic therapy for triple negative breast cancer.Materials today. Bio · 2025Article
- Adaptation of the Spalax galili transcriptome to hypoxia may underlie the complex phenotype featuring longevity and cancer resistance.npj aging · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics.Cell reports · 2025Article
- Looping forward: exploring R-loop processing and therapeutic potential.FEBS letters · 2025Review
- The hidden architects of the genome: a comprehensive review of R-loops.Molecular biology reports · 2024Review
- Senataxin mediates R-loop resolution on HPV episomes.Journal of virology · 2024Article
- Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.The Journal of cell biology · 2024Article
- Genomics of post-bottleneck recovery in the northern elephant seal.Nature ecology & evolution · 2024Article
- Role of Senataxin in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2023Review
- Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops.Nucleic acids research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.
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Registered trials
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.