ArticleMolecular cancer research : MCR2014
Hypoxic stress facilitates acute activation and chronic downregulation of fanconi anemia proteins.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Efficacy and safety of PARP inhibitors in advanced or recurrent endometrial cancer: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.Gynecologic oncology · 2022Trial
- Essential genetic mutations impair DNA damage repair and modulate tumor immune microenvironment in ccRCC.MedScience · 2026Review
- Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.Frontiers in cell and developmental biology · 2023Article
- Genome ofInternational journal of molecular sciences · 2022Article
- Crypt and Villus Transcriptomic Responses in Mouse Small Intestine Following Oral Exposure to Hexavalent Chromium.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Clear cell renal cell carcinoma ontogeny and mechanisms of lethality.Nature reviews. Nephrology · 2021Review
- Tumor Hypoxia Drives Genomic Instability.Frontiers in cell and developmental biology · 2021Review
- Article
- Human 2-oxoglutarate-dependent oxygenases: nutrient sensors, stress responders, and disease mediators.Biochemical Society transactions · 2020Review
- In utero exposure to transient ischemia-hypoxemia promotes long-term neurodevelopmental abnormalities in male rat offspring.JCI insight · 2020Article
- Impact of hypoxia on DNA repair and genome integrity.Mutagenesis · 2020Review
- Inside the hypoxic tumour: reprogramming of the DDR and radioresistance.Cell death discovery · 2020Review
- Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51.Science translational medicine · 2019Article
- Fanconi anemia protein FANCI functions in ribosome biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- PTEN Regulates Nonhomologous End Joining By Epigenetic Induction of NHEJ1/XLF.Molecular cancer research : MCR · 2018Article
- Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: A NCI clinical trials planning meeting report.Gynecologic oncology · 2018Review
- Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity inOncotarget · 2018Article
- Anti-tumor Activity of miniPEG-γ-Modified PNAs to Inhibit MicroRNA-210 for Cancer Therapy.Molecular therapy. Nucleic acids · 2017Article
- Hypoxia tolerance, longevity and cancer-resistance in the mole rat Spalax - a liver transcriptomics approach.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledHypoxia induces genomic instability through replication stress and dysregulation of vital DNA repair pathways. The Fanconi anemia (FA) proteins, FANCD2 and FANCI, are key members of a DNA repair pathway that responds to replicative stress, suggesting that they undergo regulation by hypoxic conditions. Here acute hypoxic stress activates the FA pathway via ubiquitination of FANCD2 and FANCI in an ATR-dependent manner. In addition, the presence of an intact FA pathway is required for preventing hypoxia-induced DNA damage measurable by the comet assay, limiting the accumulation of γH2AX (a marker of DNA damage or stalled replication), and protecting cells from hypoxia-induced apoptosis. Furthermore, prolonged hypoxia induces transcriptional repression of FANCD2 in a manner analogous to the hypoxic downregulation of BRCA1 and RAD51. Thus, hypoxia-induced FA pathway activation plays a key role in maintaining genome integrity and cell survival, while FA protein downregulation with prolonged hypoxia contributes to genomic instability. IMPLICATIONS: This work highlights the critical role of the FA pathway in response to hypoxic stress and identifies the pathway as a therapeutic target under hypoxic conditions.
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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.