ArticleNature communications2020
BRD4 prevents the accumulation of R-loops and protects against transcription-replication collision events and DNA damage.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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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.
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Who cites it
105 citing papers in PubMed, 146 citations in OpenAlex.
- The DNA/RNA Helicase SETX Maintains R-Loop Homeostasis to Promote Chemoresistance in Ovarian Cancer.Cancer science · 2026Article
- Focal ischemia induces genome-wide accumulation of R-loops in the brain.Molecular therapy. Nucleic acids · 2026Article
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.International journal of molecular sciences · 2026Review
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- R-PLA enables enhanced detection of R-loops in mammalian cells using proximity ligation.Cell reports methods · 2026Article
- MuRaL-indel: a deep learning framework for building insertion and deletion mutation rate maps.Briefings in bioinformatics · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Direct Readout of Multivalent Chromatin Reader-Nucleosome Interactions by Nucleosome Mass Spectrometry.ACS central science · 2026Article
- Crosstalk Between R-Loops, RNA/DNA Modifications, and Cell Death Dynamics in Canine Models of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Macrophage sensing of the acidic milieu: BRD4 condensates in focus.Life metabolism · 2026Article
- 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
- Cocaine-Induced Changes in the BRD4 Interactome Identifies Casein Kinase 1 Epsilon as a Therapeutic Target.Journal of neurochemistry · 2026Article
- Hsa_circ_0030568 Promotes the Proliferation and Migration of Prostate Cancer CellsCombinatorial chemistry & high throughput screening · 2026Article
- R‑loops in hepatocellular carcinoma: Bridging genomic instability and therapeutic opportunity (Review).Molecular medicine reports · 2026Review
- BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.Science advances · 2025Article
- A mitotic bookmark coordinates transcription and replication in Drosophila embryos.Nucleic acids research · 2025Article
- Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Untargeted Diversity-Oriented Synthesis for the Discovery of New Antitumor Agents: An Integrated Approach of Inverse Virtual Screening, Bioinformatics, and Omics for Target Deconvolution.Journal of medicinal chemistry · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Proper chromatin function and maintenance of genomic stability depends on spatiotemporal coordination between the transcription and replication machinery. Loss of this coordination can lead to DNA damage from increased transcription-replication collision events. We report that deregulated transcription following BRD4 loss in cancer cells leads to the accumulation of RNA:DNA hybrids (R-loops) and collisions with the replication machinery causing replication stress and DNA damage. Whole genome BRD4 and γH2AX ChIP-Seq with R-loop IP qPCR reveals that BRD4 inhibition leads to accumulation of R-loops and DNA damage at a subset of known BDR4, JMJD6, and CHD4 co-regulated genes. Interference with BRD4 function causes transcriptional downregulation of the DNA damage response protein TopBP1, resulting in failure to activate the ATR-Chk1 pathway despite increased replication stress, leading to apoptotic cell death in S-phase and mitotic catastrophe. These findings demonstrate that inhibition of BRD4 induces transcription-replication conflicts, DNA damage, and cell death in oncogenic cells.
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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.