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A microchip platform for structural oncology applications.

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dc.contributor.authorWinton, Carly E.en
dc.contributor.authorGilmore, Brian L.en
dc.contributor.authorDemmert, Andrew C.en
dc.contributor.authorKarageorge, Vasileaen
dc.contributor.authorSheng, Zhien
dc.contributor.authorKelly, Deborah F.en
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentBiomedical Engineering and Sciencesen
dc.date.accessioned2017-03-24T17:55:39Zen
dc.date.available2017-03-24T17:55:39Zen
dc.date.issued2016en
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
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/npjbcancer.2016.16en
dc.identifier.urihttp://hdl.handle.net/10919/76673en
dc.identifier.volume2en
dc.language.isoenen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27583302en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titleA microchip platform for structural oncology applications.en
dc.title.serialNPJ Breast Canceren
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen

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