1. Molecular Analysis of BRCA1 in Human Breast Cancer Cells Under Oxidative Stress.
- Author
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Gilmore BL, Liang Y, Winton CE, Patel K, Karageorge V, Varano AC, Dearnaley W, Sheng Z, and Kelly DF
- Subjects
- BRCA1 Protein genetics, BRCA1 Protein metabolism, BRCA2 Protein genetics, BRCA2 Protein metabolism, Binding Sites, Cell Line, Tumor, DNA Damage, Female, Guanine analogs & derivatives, Guanine metabolism, Humans, Hydrogen Peroxide pharmacology, Mammary Glands, Human drug effects, Mammary Glands, Human metabolism, Mammary Glands, Human pathology, Models, Molecular, Molecular Imaging, Mutation, Oxidative Stress, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Structural Homology, Protein, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, BRCA1 Protein chemistry, DNA Repair, Gene Expression Regulation, Neoplastic, Tumor Suppressor Proteins chemistry, Ubiquitin-Protein Ligases chemistry
- Abstract
The precise manner in which physical changes to the breast cancer susceptibility protein (BRCA1) affect its role in DNA repair events remain unclear. Indeed, cancer cells harboring mutations in BRCA1 suffer from genomic instability and increased DNA lesions. Here, we used a combination of molecular imaging and biochemical tools to study the properties of the BRCA1 in human cancer cells. Our results reveal new information for the manner in which full-length BRCA1 engages its binding partner, the BRCA1-associated Ring Domain protein (BARD1) under oxidative stress conditions. We also show how physical differences between wild type and mutated BRCA1
5382insC impact the cell's response to oxidative damage. Overall, we demonstrate how clinically relevant changes to BRCA1 affect its structure-function relationship in hereditary breast cancer.- Published
- 2017
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