ArticleJournal of radiation research2024
Phase-separated super-enhancers confer an innate radioresistance on genomic DNA.
Article in Journal of radiation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
5 citing papers in PubMed.
- Liquid-liquid phase separation in cancer: oncogenic roles, therapeutic potential, and epigenetic regulation.Molecular biology reports · 2026Review
- Role of the Super-Enhancer Component Bromodomain Protein 4 in the Radiation Response of Human Head and Neck Squamous Cell Carcinoma Cells.Current issues in molecular biology · 2026Article
- Nanoscale Analysis beyond Imaging by Atomic Force Microscopy: Molecular Perspectives on Oncology and Neurodegeneration.Small science · 2025Review
- Review
- Liquid-liquid phase separation in super enhancer-driven oncogenesis: mechanisms, immune evasion, and therapeutic implications.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Recently, biomolecular condensates formed through liquid-liquid phase separation have been widely reported to regulate key intracellular processes involved in cell biology and pathogenesis. BRD4 is a nuclear protein instrumental to the establishment of phase-separated super-enhancers (SEs) to direct the transcription of important genes. We previously observed that protein droplets of BRD4 became hydrophobic as their size increase, implying an ability of SEs to limit the ionization of water molecules by irradiation. Here, we aim to establish if SEs confer radiation resistance in cancer cells. We established an in vitro DNA damage assay that measures the effect of radicals provoked by the Fenton reaction on DNA integrity. This revealed that DNA damage was markedly reduced when BRD4 underwent phase separation with DNA. Accordingly, co-focal imaging analyses revealed that SE foci and DNA damage foci are mutually exclusive in irradiated cells. Lastly, we observed that the radioresistance of cancer cells was significantly reduced when irradiation was combined with ARV-771, a BRD4 de-stabilizer. Our data revealed the existence of innately radioresistant genomic regions driven by phase separation in cancer cells. The disruption of these phase-separated components enfolding genomic DNA may represent a novel strategy to augment the effects of radiotherapy.
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Registered trials
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