Molecular Analysis of BRCA1 in Human Breast Cancer Cells under Oxidative Stress

Brian L. Gilmore, Yanping Liang, Carly E. Winton, Kaya Patel, Vasilea Karageorge, A. Cameron Varano, William Dearnaley, Zhi Sheng, Deborah F. Kelly

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article number43435
JournalScientific reports
Volume7
DOIs
StatePublished - Mar 6 2017

All Science Journal Classification (ASJC) codes

  • General

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