ArticleNature structural & molecular biology2013
A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization.
Article in Nature structural & molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 100 citations in OpenAlex.
- HELZ-BRCA2 complex resolves R-loops to drive transcription-coupled homologous recombination.Nature communications · 2026Article
- A germlineScience advances · 2025Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- Particulate hexavalent chromium exposure induces DNA double-strand breaks and inhibits homologous recombination repair in rat and human lung tissues.Chemosphere · 2025Article
- Trypanosomatid DRBD9s are likely to be eIF4B orthologues.Journal of biosciences · 2025Article
- Tumorigenesis Caused by Aberrant Expression of GANP, a Central Component in the Mammalian TREX-2 Complex-Lessons from Transcription-Coupled DNA Damages.International journal of molecular sciences · 2024Review
- DSS1 restrains BRCA2's engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis.Nature communications · 2024Article
- The BRCA2 R2645G variant increases DNA binding and induces hyper-recombination.Nucleic acids research · 2024Article
- Differential impact of cytoplasmic vs. nuclear RAD51 expression on breast cancer progression and patient prognosis.International journal of oncology · 2024Article
- Regulatory elements inGenetics in medicine open · 2024Article
- Characterization of BRCA2 R3052Q variant in mice supports its functional impact as a low-risk variant.Cell death & disease · 2023Article
- Prolonged particulate hexavalent chromium exposure induces RAD51 foci inhibition and cytoplasmic accumulation in immortalized and primary human lung bronchial epithelial cells.Toxicology and applied pharmacology · 2023Article
- CRISPR/Cas9-Targeted Disruption of Two Highly HomologousInternational journal of molecular sciences · 2023Article
- Fanconi anemia caused by biallelic inactivation of BRCA2 can present with an atypical cancer phenotype in adulthood.Clinical genetics · 2023Article
- Human RAD51 Protein Forms Amyloid-like AggregatesInternational journal of molecular sciences · 2022Article
- Article
- The Mechanistic Understanding of RAD51 Defibrillation: A Critical Step in BRCA2-Mediated DNA Repair by Homologous Recombination.International journal of molecular sciences · 2022Article
- Dynamic interaction of BRCA2 with telomeric G-quadruplexes underlies telomere replication homeostasis.Nature communications · 2022Article
- Evidence for reduced BRCA2 functional activity in Homo sapiens after divergence from the chimpanzee-human last common ancestor.Cell reports · 2022Article
- The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus.Frontiers in genetics · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Germline missense mutations affecting a single BRCA2 allele predispose humans to cancer. Here we identify a protein-targeting mechanism that is disrupted by the cancer-associated mutation, BRCA2(D2723H), and that controls the nuclear localization of BRCA2 and its cargo, the recombination enzyme RAD51. A nuclear export signal (NES) in BRCA2 is masked by its interaction with a partner protein, DSS1, such that point mutations impairing BRCA2-DSS1 binding render BRCA2 cytoplasmic. In turn, cytoplasmic mislocalization of mutant BRCA2 inhibits the nuclear retention of RAD51 by exposing a similar NES in RAD51 that is usually obscured by the BRCA2-RAD51 interaction. Thus, a series of NES-masking interactions localizes BRCA2 and RAD51 in the nucleus. Notably, BRCA2(D2723H) decreases RAD51 nuclear retention even when wild-type BRCA2 is also present. Our findings suggest a mechanism for the regulation of the nucleocytoplasmic distribution of BRCA2 and RAD51 and its impairment by a heterozygous disease-associated mutation.
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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.