ArticleRadiation research2010
Impact of RING and BRCT domain mutations on BRCA1 protein stability, localization and recruitment to DNA damage.
Article in Radiation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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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
19 citing papers in PubMed, 40 citations in OpenAlex.
- Hybrid-seq deciphers the complex transcriptional profile of the humanRNA biology · 2023Article
- Molecular-Targeted Therapy for Tumor-Agnostic Mutations in Acute Myeloid Leukemia.Biomedicines · 2022Review
- PARP Inhibitors: Clinical Limitations and Recent Attempts to Overcome Them.International journal of molecular sciences · 2022Review
- How does re-classification of variants of unknown significance (VUS) impact the management of patients at risk for hereditary breast cancer?BMC medical genomics · 2022Article
- Identification of the most common BRCA alterations through analysis of germline mutation databases: Is droplet digital PCR an additional strategy for the assessment of such alterations in breast and ovarian cancer families?International journal of oncology · 2022Article
- Impact of a Single Nucleotide Polymorphism on the 3D Protein Structure and Ubiquitination Activity of E3 Ubiquitin Ligase Arkadia.Frontiers in molecular biosciences · 2022Article
- The BRCA1/BARD1 ubiquitin ligase and its substrates.The Biochemical journal · 2021Review
- BBIT20 inhibits homologous DNA repair with disruption of the BRCA1-BARD1 interaction in breast and ovarian cancer.British journal of pharmacology · 2021Article
- Exploiting DNA Damage Repair in Precision Cancer Therapy: BRCA1 as a Prime Therapeutic Target.Cancers · 2021Review
- The contribution of large genomic rearrangements in BRCA1 and BRCA2 to South African familial breast cancer.BMC cancer · 2020Article
- Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: review of radiosensitivity assays.Biological procedures online · 2020Review
- Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets.Frontiers in cell and developmental biology · 2020Review
- Article
- Review
- Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer.Annual review of cancer biology · 2018Article
- Mutational analysis ofMolecular genetics & genomic medicine · 2017Article
- A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer.BMC medical genomics · 2016Article
- Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks.Human mutation · 2015Article
- In Vitro Enhanced Sensitivity to Cisplatin in D67Y BRCA1 RING Domain Protein.Breast cancer : basic and clinical research · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations within the tumor suppressor BRCA1 cause the majority of hereditary breast and ovarian cancers. The BRCA1 protein is an important regulator of DNA double-strand break repair, and BRCA1-deficient cells are highly sensitive to ionizing radiation. Furthermore, BRCA1 function may contribute to enforcement of the G(2) cell cycle checkpoint. E3-ubiquitin ligase activity is the only known enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger domain. The C-terminal BRCT repeat domain, which mediates protein-protein interactions, is the only other identified structural domain. By investigating cancer-linked mutations within each domain, we demonstrate that truncation of the BRCT domain greatly impairs the stability and nuclear localization of BRCA1 protein. A missense mutation within the RING domain does not affect these biochemical properties. However, both mutant forms of BRCA1 fail to colocalize in nuclear foci with the known BRCA1-interacting proteins BARD1 and BACH1, which are important for DNA repair. This failure occurs despite the continued ability of the RING mutant protein to interact with BACH1 and the ability of the BRCT mutant to interact with BARD1. Furthermore, neither mutant form of BRCA1 is recruited into DNA damage-associated foci marked by gamma-H2AX. Therefore, our data suggest that both the RING and BRCT domains of BRCA1 are required for an early step in the function of BRCA1 during DNA repair: recruitment to the sites of DNA damage.
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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.