title: 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 BRCA15382insCimpact 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.
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Gilmore
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.|School of Biomedical Engineering and Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Carly E
authors.initials: CE
authors.lastname: Winton
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
authors.forename: Kaya
authors.initials: K
authors.lastname: Patel
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
authors.forename: Vasilea
authors.initials: V
authors.lastname: Karageorge
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.|Translational Biology, Medicine, and Health Graduate Program, Virginia Tech, Blacksburg VA, USA.
authors.forename: A Cameron
authors.initials: AC
authors.lastname: Varano
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Dearnaley
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.|School of Biomedical Engineering and Science, Virginia Tech, Blacksburg, VA, USA.|Virginia Tech Carilion School of Medicine, Virginia Tech, Roanoke, VA, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.|School of Biomedical Engineering and Science, Virginia Tech, Blacksburg, VA, USA.|Virginia Tech Carilion School of Medicine, Virginia Tech, Roanoke, VA, USA.|Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Kelly
mesh_terms: D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D057054:Molecular Imaging; D009154:Mutation; D018384:Oxidative Stress; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D040681:Structural Homology, Protein; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D025521:Tumor Suppressor Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D006861:Hydrogen Peroxide; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases