ArticleNucleic acids research2023
RNF8 ubiquitylation of XRN2 facilitates R-loop resolution and restrains genomic instability in BRCA1 mutant cells.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- The DNA/RNA Helicase SETX Maintains R-Loop Homeostasis to Promote Chemoresistance in Ovarian Cancer.Cancer science · 2026Article
- Article
- PAF1c depletion confers chemoresistance to topoisomerase inhibitors.Cell insight · 2026Article
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- Finding novel vulnerabilities of hypomorphic BRCA1 alleles.Molecular oncology · 2026Article
- NELF prevents transcriptional readthrough into DNA replication zones in cancer cells.EMBO reports · 2026Article
- Paradoxical oncogenic effects of hepatic Brca1 through modulating Bhmt.Scientific reports · 2026Article
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Intranuclear paraspeckle-circular RNA TACC3 assembly forms RNA-DNA hybrids to facilitate MASH-related hepatocellular carcinoma growth in an mCancer communications (London, England) · 2025Article
- Nuclear-Localized BCKDK Facilitates Homologous Recombination Repair to Support Breast Cancer Progression and Therapy Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Recent Overview of Molecular Pathways in Synthetic Lethality as a Proposed Valid Target in Oncology: Current Insights and Future Directions.Indian journal of surgical oncology · 2025Review
- KRT80, Regulated by RNF8-Mediated Ubiquitination, Contributes to Glucose Metabolic Reprogramming and Progression of Glioblastoma.Neurochemical research · 2025Article
- Histone Phosphorylation in DNA Damage Response.International journal of molecular sciences · 2025Review
- SART3 promotes homologous recombination repair by stimulating DNA-RNA hybrids removal and DNA end resection.Nature communications · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
- Looping forward: exploring R-loop processing and therapeutic potential.FEBS letters · 2025Review
- Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis.Nature communications · 2024Article
- Molecular Basis of XRN2-Deficient Cancer Cell Sensitivity to Poly(ADP-ribose) Polymerase Inhibition.Cancers · 2024Article
- Article
Corrections and comments
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Authors and funding
33 authors at 8 institutions in 4 countries.
Funding
Abstract
Breast cancer linked with BRCA1/2 mutations commonly recur and resist current therapies, including PARP inhibitors. Given the lack of effective targeted therapies for BRCA1-mutant cancers, we sought to identify novel targets to selectively kill these cancers. Here, we report that loss of RNF8 significantly protects Brca1-mutant mice against mammary tumorigenesis. RNF8 deficiency in human BRCA1-mutant breast cancer cells was found to promote R-loop accumulation and replication fork instability, leading to increased DNA damage, senescence, and synthetic lethality. Mechanistically, RNF8 interacts with XRN2, which is crucial for transcription termination and R-loop resolution. We report that RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone genomic loci and that RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, thereby promoting R-loop accumulation, transcription-replication collisions, excessive genomic instability, and cancer cell death. Collectively, our work identifies a synthetic lethal interaction between RNF8 and BRCA1, which is mediated by a pathological accumulation of R-loops.
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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.