ArticleNucleic acids research2023
Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Telomere-driven replicative crisis is driven by large-scale changes in genomic architecture.Genome research · 2026Article
- Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- HIF-1-regulated TPM3 links hypoxia to motility and invasion beyond the hypoxic fraction in triple-negative breast cancer.NPJ breast cancer · 2026Article
- A guide to reactive oxygen species in tumour hypoxia: measurement and therapeutic implications.Molecular oncology · 2025Review
- PVC Nanoplastics Exposure Exacerbates Asthma through R-Loop Accumulation and Subsequent STING Activation in Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma.Cell communication and signaling : CCS · 2025Article
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.Nucleic acids research · 2025Article
- Role of Oxidative Stress in the Occurrence, Development, and Treatment of Breast Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS-STING pathway.Open medicine (Warsaw, Poland) · 2025Article
- Hypoxia promotes histone H3K9 lactylation to enhanceiScience · 2024Article
- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia is a common feature of solid tumors and is associated with poor patient prognosis, therapy resistance and metastasis. Radiobiological hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response and the unfolded protein response. Recently, we found that hypoxia also leads to the robust accumulation of R-loops, which led us to question here both the mechanism and consequence of hypoxia-induced R-loops. Interestingly, we found that the mechanism of R-loop accumulation in hypoxia is dependent on non-DNA damaging levels of reactive oxygen species. We show that hypoxia-induced R-loops play a critical role in the transcriptional stress response, evidenced by the repression of ribosomal RNA synthesis and the translocation of nucleolin from the nucleolus into the nucleoplasm. Upon depletion of R-loops, we observed a rescue of both rRNA transcription and nucleolin translocation in hypoxia. Mechanistically, R-loops accumulate on the rDNA in hypoxia and promote the deposition of heterochromatic H3K9me2 which leads to the inhibition of Pol I-mediated transcription of rRNA. These data highlight a novel mechanistic insight into the hypoxia-induced transcriptional stress response through the ROS-R-loop-H3K9me2 axis. Overall, this study highlights the contribution of transcriptional stress to hypoxia-mediated tumorigenesis.
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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 Socratic graph.