ArticleNature communications2017
BRCA2 antagonizes classical and alternative nonhomologous end-joining to prevent gross genomic instability.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 52 citations in OpenAlex.
- Single-Cell Circulating Tumor Cell Analysis Reveals Genomic Instability as a Distinctive Feature of Aggressive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Pan-Cancer Genomic Scars of Alternative End Joining and Single-Strand Annealing.bioRxiv : the preprint server for biology · 2026Article
- Discovery of Two Structurally Distinct Classes of Inhibitors Targeting the Nuclease MUS81 and Enhancing Efficacy of Chemotherapy in Cancer Cells.Journal of medicinal chemistry · 2026Article
- Review
- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- TGF-β superfamily-induced transcriptional activation pathways establish the RAD52-dependent ALT machinery during malignant transformation of MPNSTs.Scientific reports · 2024Article
- Inhibition of Aberrantly Overexpressed Polo-like Kinase 4 Is a Potential Effective Treatment for DNA Damage Repair-Deficient Uterine Leiomyosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Quantitative, titratable and high-throughput reporter assays to measure DNA double strand break repair activity in cells.Nucleic acids research · 2024Article
- Gene expression of non-homologous end-joining pathways in the prognosis of ovarian cancer.iScience · 2023Article
- In vivo reduction of RAD51-mediated homologous recombination triggers aging but impairs oncogenesis.The EMBO journal · 2023Article
- Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants.PLoS genetics · 2023Article
- Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The splicing factor SNRPB promotes ovarian cancer progression through regulating aberrant exon skipping of POLA1 and BRCA2.Oncogene · 2023Article
- Noncanonical Roles of RAD51.Cells · 2023Review
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
- Essential role of theBiotechnologia · 2023Article
- Role of EMT in the DNA damage response, double-strand break repair pathway choice and its implications in cancer treatment.Cancer science · 2022Review
- Multifaceted regulation and functions of 53BP1 in NHEJ‑mediated DSB repair (Review).International journal of molecular medicine · 2022Review
- RAD51 protects against nonconservative DNA double-strand break repair through a nonenzymatic function.Nucleic acids research · 2022Article
- Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs.Stem cells (Dayton, Ohio) · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRCA2-deficient cells exhibit gross genomic instability, but the underlying mechanisms are not fully understood. Here we report that inactivation of BRCA2 but not RAD51 destabilizes RPA-coated single-stranded DNA (ssDNA) structures at resected DNA double-strand breaks (DSBs) and greatly enhances the frequency of nuclear fragmentation following cell exposure to DNA damage. Importantly, these BRCA2-associated deficits are fueled by the aberrant activation of classical (c)- and alternative (alt)- nonhomologous end-joining (NHEJ), and rely on the well-defined DNA damage signaling pathway involving the pro-c-NHEJ factor 53BP1 and its downstream effector RIF1. We further show that the 53BP1-RIF1 axis promotes toxic end-joining events via the retention of Artemis at DNA damage sites. Accordingly, loss of 53BP1, RIF1, or Artemis prolongs the stability of RPA-coated DSB intermediates in BRCA2-deficient cells and restores nuclear integrity. We propose that BRCA2 antagonizes 53BP1, RIF1, and Artemis-dependent c-NHEJ and alt-NHEJ to prevent gross genomic instability in a RAD51-independent manner.
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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.