Insights from three decades of BRCA1/2 modeling in mice.

No abstract is available for this paper.

• Publication year

  2026

• Venue

  Nature Genetics

• Publication date

  2026-01-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41588-025-02448-zPMID 41495480
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer

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• BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair.

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• Mechanisms that clear mutations drive field cancerization in mammary tissue

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• A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer

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• Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors

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• Genetic separation of Brca1 functions reveal mutation-dependent Polθ vulnerabilities

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• Loss of the Volume-regulated Anion Channel Components LRRC8A and LRRC8D Limits Platinum Drug Efficacy

  2022cited by this paper
• STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer

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• Loss of Nuclear DNA Ligase III Reverts PARP Inhibitor Resistance in BRCA1/53BP1 Double-deficient Cells by Exposing ssDNA Gaps

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• RNF168 regulates R-loop resolution and genomic stability in BRCA1/2-deficient tumors.

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• A first-in-class Polymerase Theta Inhibitor selectively targets Homologous-Recombination-Deficient Tumors

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• RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage

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• Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance

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• Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors

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• A BRCA1 Coiled-Coil Domain Variant Disrupting PALB2 Interaction Promotes the Development of Mammary Tumors and Confers a Targetable Defect in Homologous Recombination Repair

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• Ablation of the Brca1–Palb2 Interaction Phenocopies Fanconi Anemia in Mice

  2020cited by this paper
• 53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice

  2020cited by this paper
• Genetically defined syngeneic mouse models of ovarian cancer as tools for the discovery of combination immunotherapy.

  2020cited by this paper
• Clinical BRCA1/2 reversion analysis identifies hotspot mutations and predicted neoantigens associated with therapy resistance.

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• BRCA1 Mutational Complementation Induces Synthetic Viability.

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• Tissue-Specific Carcinogens as Soil to Seed BRCA1/2-Mutant Hereditary Cancers.

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• PARP Inhibitor Efficacy Depends on CD8+ T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer.

  2019cited by this paper
• BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation.

  2019cited by this paper
• Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer

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• BRCA2 Regulates Transcription Elongation by RNA Polymerase II to Prevent R-Loop Accumulation

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• BRCA1‐associated mammary tumorigenesis is dependent on estrogen rather than progesterone signaling

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• PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer

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• The BRCT Domains of the BRCA1 and BARD1 Tumor Suppressors Differentially Regulate Homology-Directed Repair and Stalled Fork Protection.

  2018cited by this paper
• Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality.

  2018cited by this paper
• The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells

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• Radiosensitivity is an acquired vulnerability of PARPi-resistant BRCA1-deficient tumors

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• Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer

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• Selected Alkylating Agents Can Overcome Drug Tolerance of G0-like Tumor Cells and Eradicate BRCA1-Deficient Mammary Tumors in Mice

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• Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis

  2017cited by this paper
• Interaction with PALB2 Is Essential for Maintenance of Genomic Integrity by BRCA2

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• Persistent Activation of NF-κB in BRCA1-Deficient Mammary Progenitors Drives Aberrant Proliferation and Accumulation of DNA Damage.

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• RANKL/RANK control Brca1 mutation-driven mammary tumors

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• Prophylactic window therapy with the clinical poly(ADP‐ribose) polymerase inhibitor olaparib delays BRCA1‐deficient mammary tumour formation in mice

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• RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers

  2016cited by this paper
• Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation

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• BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1.

  2016cited by this paper
• Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer.

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  2015cited by this paper
• BRCA1 Recruitment to Transcriptional Pause Sites Is Required for R-Loop-Driven DNA Damage Repair

  2015cited by this paper
• Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination

  2015cited by this paper
• Homologous recombination-deficient tumors are hyper-dependent on POLQ-mediated repair

  2015cited by this paper
• REV7 counteracts DNA double-strand break resection and affects PARP inhibition

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• BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis

  2014cited by this paper
• Estrogen controls the survival of BRCA1-deficient cells via a PI3K–NRF2-regulated pathway

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• BRCA1 haploinsufficiency for replication stress suppression in primary cells

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• The PARP Inhibitors, Veliparib and Olaparib, Are Effective Chemopreventive Agents for Delaying Mammary Tumor Development in BRCA1-deficient Mice

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  2013cited by this paper
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  2012cited by this paper
• Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.

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• Cooperativity of Rb, Brca1, and p53 in Malignant Breast Cancer Evolution

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  2010cited by this paper
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• A High-Throughput Pharmaceutical Screen Identifies Compounds with Specific Toxicity against BRCA2-Deficient Tumors

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  2007cited by this paper
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• ATM–Chk2–p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency

  2006cited by this paper
• Hyperplasia and Spontaneous Tumor Development in the Gynecologic System in Mice Lacking the BRCA1-Δ11 Isoform

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• Prevention of Brca1-Mediated Mammary Tumorigenesis in Mice by a Progesterone Antagonist

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• Homozygous germ line mutation in exon 27 of murine Brca2 disrupts the Fancd2–Brca2 pathway in the homologous recombination‐mediated DNA interstrand cross‐links' repair but does not affect meiosis

  2005cited by this paper
• BRCA2 deficiency in mice leads to meiotic impairment and infertility

  2004cited by this paper
• Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein.

  2003cited by this paper
• Normal lymphocyte development and thymic lymphoma formation in Brca1 exon-11-deficient mice

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• Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice

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• Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.

  2002cited by this paper
• Cancer susceptibility of mice with a homozygous deletion in the COOH-terminal domain of the Brca2 gene.

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• Development of mammary adenocarcinomas by tissue-specific knockout of Brca2 in mice

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• Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis

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• Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer

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• Tumorigenesis in mice carrying a truncating Brca1 mutation.

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• Mutation in Brca2 stimulates error‐prone homology‐directed repair of DNA double‐strand breaks occurring between repeated sequences

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• Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation

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