ArticleNucleic acids research2019
BRCA1-associated R-loop affects transcription and differentiation in breast luminal epithelial cells.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Decoding chromatin-associated RNA (caRNA) interaction networks: from genome-wide dynamic capture to epigenetic mechanisms in plants and animals.Epigenetics · 2026Review
- Genome-wide mapping reveals increased R-loops in topoisomerase III-beta-deficient human cells.iScience · 2026Article
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- The role of non-coding variants in hereditary cancer syndromes: mechanistic insights and clinical implications.Annals of medicine and surgery (2012) · 2026Review
- Resolution of R-loops and transcription-replication conflicts by SETX-BRCA1-BARD1 complex.Nature structural & molecular biology · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- BRCA1: An Unrecognized Modulator of Lineage Plasticity in Basal-like Breast Cancer.Journal of mammary gland biology and neoplasia · 2025Review
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance.Science advances · 2025Article
- Lamin A/C Deficiency Drives Genomic Instability and Poor Survival in Small-Cell Lung Cancer through Increased R-loop Accumulation.bioRxiv : the preprint server for biology · 2025Article
- PCAF promotes R-loop resolution via histone acetylation.Nucleic acids research · 2024Article
- R-loop functions inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.Nature communications · 2024Article
- Bridging the gap: R-loop mediated genomic instability and its implications in neurological diseases.Epigenomics · 2024Review
- ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress.Nucleic acids research · 2024Article
- BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.International journal of molecular sciences · 2023Review
- The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers.Asian Pacific journal of cancer prevention : APJCP · 2023Review
- C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption.Nature communications · 2023Article
- In Silico Identification of a BRCA1:miR-29:DNMT3 Axis Involved in the Control of Hormone Receptors in BRCA1-Associated Breast Cancers.International journal of molecular sciences · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
BRCA1-associated basal-like breast cancer originates from luminal progenitor cells. Breast epithelial cells from cancer-free BRCA1 mutation carriers are defective in luminal differentiation. However, how BRCA1 deficiency leads to lineage-specific differentiation defect is not clear. BRCA1 is implicated in resolving R-loops, DNA-RNA hybrid structures associated with genome instability and transcriptional regulation. We recently showed that R-loops are preferentially accumulated in breast luminal epithelial cells of BRCA1 mutation carriers. Here, we interrogate the impact of a BRCA1 mutation-associated R-loop located in a putative transcriptional enhancer upstream of the ERα-encoding ESR1 gene. Genetic ablation confirms the relevance of this R-loop-containing region to enhancer-promoter interactions and transcriptional activation of the corresponding neighboring genes, including ESR1, CCDC170 and RMND1. BRCA1 knockdown in ERα+ luminal breast cancer cells increases intensity of this R-loop and reduces transcription of its neighboring genes. The deleterious effect of BRCA1 depletion on transcription is mitigated by ectopic expression of R-loop-removing RNase H1. Furthermore, RNase H1 overexpression in primary breast cells from BRCA1 mutation carriers results in a shift from luminal progenitor cells to mature luminal cells. Our findings suggest that BRCA1-dependent R-loop mitigation contributes to luminal cell-specific transcription and differentiation, which could in turn suppress BRCA1-associated tumorigenesis.
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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.