ArticleNucleic acids research2021
Cancer-causing BRCA2 missense mutations disrupt an intracellular protein assembly mechanism to disable genome maintenance.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Reclassification ofCurrent oncology (Toronto, Ont.) · 2026Article
- Ultra-rare functional variants reveal early-onset breast cancer risk genes and pathways in the UK Biobank and All of Us Research Program.American journal of human genetics · 2026Article
- Moss BRCA2 lacking the canonical DNA-binding domain promotes homologous recombination and binds to DNA.Nucleic acids research · 2025Article
- Global research trends in PARP inhibitors for ovarian cancer: a bibliometric analysis.Discover oncology · 2025Article
- Predicted functional consequences of WNT ligand mutations in colorectal cancer.Biophysical journal · 2025Article
- The BRCA2 R2645G variant increases DNA binding and induces hyper-recombination.Nucleic acids research · 2024Article
- Gsw-fi: a GLM model incorporating shrinkage and double-weighted strategies for identifying cancer driver genes with functional impact.BMC bioinformatics · 2024Article
- Characterization of BRCA2 R3052Q variant in mice supports its functional impact as a low-risk variant.Cell death & disease · 2023Article
- Phosphorylation of Schizosaccharomyces pombe Dss1 mediates direct binding to the ubiquitin-ligase Dma1 in vitro.Protein science : a publication of the Protein Society · 2023Article
- Repair of DNA double-strand breaks in plant meiosis: role of eukaryotic RecA recombinases and their modulators.Plant reproduction · 2023Review
- Refinement of the assignment to the ACMG/AMP BS3 and PS3 criteria of eightFrontiers in oncology · 2023Article
- Article
- Dynamic interaction of BRCA2 with telomeric G-quadruplexes underlies telomere replication homeostasis.Nature communications · 2022Article
- BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks.Nature communications · 2022Article
- The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus.Frontiers in genetics · 2022Article
- Role of BRCA2 DNA-binding and C-terminal domain in its mobility and conformation in DNA repair.eLife · 2021Article
- Development and Verification of a Prostate Cancer Prognostic Signature Based on an Immunogenomic Landscape Analysis.Frontiers in oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Cancer-causing missense mutations in the 3418 amino acid BRCA2 breast and ovarian cancer suppressor protein frequently affect a short (∼340 residue) segment in its carboxyl-terminal domain (DBD). Here, we identify a shared molecular mechanism underlying their pathogenicity. Pathogenic BRCA2 missense mutations cluster in the DBD's helical domain (HD) and OB1-fold motifs, which engage the partner protein DSS1. Pathogenic - but not benign - DBD mutations weaken or abolish DSS1-BRCA2 assembly, provoking mutant BRCA2 oligomers that are excluded from the cell nucleus, and disable DNA repair by homologous DNA recombination (HDR). DSS1 inhibits the intracellular oligomerization of wildtype, but not mutant, forms of BRCA2. Remarkably, DSS1 expression corrects defective HDR in cells bearing pathogenic BRCA2 missense mutants with weakened, but not absent, DSS1 binding. Our findings identify a DSS1-mediated intracellular protein assembly mechanism that is disrupted by cancer-causing BRCA2 missense mutations, and suggest an approach for its therapeutic correction.
Indexed as
Identifiers
What OpenQuestion holds
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.