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Molecular Analysis of BRCA1 in Human Breast Cancer Cells Under Oxidative Stress.

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 BRCA15382insC 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.

SUBMITTER: Gilmore BL

PROVIDER: S-EPMC5338271 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Molecular Analysis of BRCA1 in Human Breast Cancer Cells Under Oxidative Stress.

Gilmore Brian L BL Liang Yanping Y Winton Carly E CE Patel Kaya K Karageorge Vasilea V Varano A Cameron AC Dearnaley William W Sheng Zhi Z Kelly Deborah F DF

Scientific reports 20170306

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 ...[more]

PMID: 28262780

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