PubMed · 8607013
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
T Beardsley. 1996. Vital data.. https://doi.org/10.1038/scientificamerican0396-100
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The tumor suppressor protein breast cancer type 1 susceptibility protein (BRCA1) plays a central role in maintaining genome stability through its involvement in DNA damage repair, transcriptional regulation, and cell-cycle control. BRCA1 functions as an obligate heterodimer with its binding partner, the BRCA1-associated RING domain protein 1 (BARD1), to coordinate accurate DNA repair. While the structured N- and C-terminal domains of BRCA1 have been well-characterized, the large central region encoded largely by exon 11 that comprises ~ 80% of the protein, is intrinsically disordered, and remains poorly structurally characterized. This intrinsically disordered region (IDR) harbors critical interaction interfaces for key proteins involved in genome maintenance, including RAD50, RAD51, MYC, and RB. Here, we report the backbone resonance assignments of a BRCA1 IDR construct spanning residues 467-696, providing a foundation for future studies aimed at understanding how the disordered central region of BRCA1 contributes to homologous recombination, interactions with BARD1, and overall BRCA1 tumor suppressor function.
Breast Cancer Gene 1 (BRCA1) is a critical regulator of genome integrity whose dysfunction greatly increases lifetime risk of breast and ovarian cancers. While BRCA1 has been extensively studied in the contexts of adult biology and cancer, its diverse functions, including homologous recombination-mediated DNA repair, cell cycle checkpoint activation, protein ubiquitination, and transcriptional regulation, have many underexplored implications. In early embryonic development, the maternal-to-zygotic transition (MZT) and subsequent developmental processes place extraordinary demands on DNA replication fidelity, cell cycle regulation, transcriptional activation, and chromatin remodeling. These critical processes overlap strikingly with canonical functions of BRCA1, yet its function in early development is poorly characterized. In this review, we investigate BRCA1 conservation across species and connect its well-established functions to findings from developmental studies to assess its role in development. We highlight evidence of BRCA1 mitigating genome integrity loss from diverse sources, maintaining the proliferative activity needed for successful germ layer formation and early tissue morphogenesis, and regulating transcription and epigenetic modifications. Together, this synthesis supports a model where BRCA1 acts as a multi-functional and dynamic regulator of early embryogenesis. Building on this, we propose outstanding questions that could further illuminate these developmental roles. Characterization of BRCA1 in early development may not only provide important insight into the origin and progression of cancer susceptibility but may also elucidate fundamental mechanisms shaping early development.
OBJECTIVE: To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis. DESIGN: Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. SETTING: A community-based case-control incidence study. SUBJECTS: Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation. MAIN OUTCOME MEASURES: Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses. RESULTS: The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (+/-SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases--50 (+/-1.4) vs 60.5 (+/-3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01). CONCLUSIONS: Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer