ArticleGenes & development2019
Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity.
Article in Genes & development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 142 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Heterozygous CECR2 variants support a distinct neurodevelopmental syndrome with features overlapping cat eye syndrome.HGG advances · 2026Article
- R-PLA enables enhanced detection of R-loops in mammalian cells using proximity ligation.Cell reports methods · 2026Article
- Cryo-EM Structure of Human ATAD2B Reveals a Hexameric Organization Contributes to ATPase Activity and Substrate Coordination.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- KAT2B-mediated epigenetic suppression of RAD51C enhances olaparib sensitivity in colorectal cancer.Cancer chemotherapy and pharmacology · 2026Article
- Loss of RanBP9 cooperates with p53 deficiency to promote sarcomagenesis.Frontiers in oncology · 2026Article
- Identification of BET inhibitors (BETi) against solitary fibrous tumor (SFT) through high-throughput screening (HTS).Neoplasia (New York, N.Y.) · 2025Article
- A mitotic bookmark coordinates transcription and replication in Drosophila embryos.Nucleic acids research · 2025Article
- PCAF-mediated acetylation regulates RAD51 dynamic localization on chromatin during HR repair.EMBO reports · 2025Article
- TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling.Molecular cell · 2025Article
- R-loops: a key driver of inflammatory responses in cancer.Experimental & molecular medicine · 2025Review
- Depletion of BRD9-mediated R-loop accumulation inhibits leukemia cell growth via transcription-replication conflict.Nucleic acids research · 2025Article
- Synergistic enhancement of PARP inhibition via small molecule UNI66-mediated suppression of BRD4-dependent transcription ofNAR cancer · 2025Article
- SWI/SNF-type complexes-transcription factor interplay: a key regulatory interaction.Cellular & molecular biology letters · 2025Review
- Article
- KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.Nature communications · 2025Article
- Regulatory role of E3 ubiquitin ligases in multiple myeloma: from molecular mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Epitranscriptome in action: RNA modifications in the DNA damage response.Molecular cell · 2024Review
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Bromodomain proteins (BRD) are key chromatin regulators of genome function and stability as well as therapeutic targets in cancer. Here, we systematically delineate the contribution of human BRD proteins for genome stability and DNA double-strand break (DSB) repair using several cell-based assays and proteomic interaction network analysis. Applying these approaches, we identify 24 of the 42 BRD proteins as promoters of DNA repair and/or genome integrity. We identified a BRD-reader function of PCAF that bound TIP60-mediated histone acetylations at DSBs to recruit a DUB complex to deubiquitylate histone H2BK120, to allowing direct acetylation by PCAF, and repair of DSBs by homologous recombination. We also discovered the bromo-and-extra-terminal (BET) BRD proteins, BRD2 and BRD4, as negative regulators of transcription-associated RNA-DNA hybrids (R-loops) as inhibition of BRD2 or BRD4 increased R-loop formation, which generated DSBs. These breaks were reliant on topoisomerase II, and BRD2 directly bound and activated topoisomerase I, a known restrainer of R-loops. Thus, comprehensive interactome and functional profiling of BRD proteins revealed new homologous recombination and genome stability pathways, providing a framework to understand genome maintenance by BRD proteins and the effects of their pharmacological inhibition.
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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.