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dc.contributor.authorWinton, Carly E.en_US
dc.contributor.authorGilmore, Brian L.en_US
dc.contributor.authorDemmert, Andrew C.en_US
dc.contributor.authorKarageorge, Vasileaen_US
dc.contributor.authorSheng, Zhien_US
dc.contributor.authorKelly, Deborah F.en_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2017-03-24T17:55:39Z
dc.date.available2017-03-24T17:55:39Z
dc.identifier.urihttp://hdl.handle.net/10919/76673
dc.description.abstractRecent advances in the development of functional materials offer new tools to dissect human health and disease mechanisms. The use of tunable surfaces is especially appealing as substrates can be tailored to fit applications involving specific cell types or tissues. Here we use tunable materials to facilitate the three-dimensional (3D) analysis of BRCA1 gene regulatory complexes derived from human cancer cells. We employed a recently developed microchip platform to isolate BRCA1 protein assemblies natively formed in breast cancer cells with and without BRCA1 mutations. The captured assemblies proved amenable to cryo-electron microscopy (EM) imaging and downstream computational analysis. Resulting 3D structures reveal the manner in which wild-type BRCA1 engages the RNA polymerase II (RNAP II) core complex that contained K63-linked ubiquitin moieties-a putative signal for DNA repair. Importantly, we also determined that molecular assemblies harboring the BRCA1(5382insC) mutation exhibited altered protein interactions and ubiquitination patterns compared to wild-type complexes. Overall, our analyses proved optimal for developing new structural oncology applications involving patient-derived cancer cells, while expanding our knowledge of BRCA1's role in gene regulatory events.en_US
dc.languageengen_US
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27583302en_US
dc.titleA microchip platform for structural oncology applications.en_US
dc.typeArticle - Refereed
dc.description.versionPublished (Publication status)en_US
dc.contributor.departmentBiological Sciencesen_US
dc.contributor.departmentFralin Biomedical Research Institute at VTCen_US
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen_US
dc.title.serialNPJ Breast Canceren_US
dc.identifier.doihttps://doi.org/10.1038/npjbcancer.2016.16
dc.identifier.volume2en_US
pubs.organisational-group/Virginia Tech
pubs.organisational-group/Virginia Tech/All T&R Faculty
pubs.organisational-group/Virginia Tech/Faculty of Health Sciences
pubs.organisational-group/Virginia Tech/University Research Institutes
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Institute


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