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Related Concept Videos

DNA Microarrays02:34

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Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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A microchip platform for structural oncology applications.

Carly E Winton1, Brian L Gilmore2, Andrew C Demmert3

  • 1Virginia Tech Carilion Research Institute, Roanoke, VA, USA ; School of Biomedical Engineering and Science, Virginia Tech, Blacksburg, VA, USA.

NPJ Breast Cancer
|September 2, 2016
PubMed
Summary
This summary is machine-generated.

Researchers used tunable materials to analyze BRCA1 gene regulatory complexes in breast cancer cells. This structural analysis revealed how BRCA1 interacts with RNA polymerase II and identified differences in mutated BRCA1, advancing structural oncology.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Functional materials offer novel approaches to study human health and disease.
  • Tunable surfaces are valuable for applications involving specific cell types or tissues.

Purpose of the Study:

  • To utilize tunable materials for the 3D structural analysis of BRCA1 gene regulatory complexes in human cancer cells.
  • To investigate the native structure and interactions of BRCA1 protein assemblies in breast cancer cells with and without BRCA1 mutations.

Main Methods:

  • Employed a microchip platform for isolating BRCA1 protein assemblies from breast cancer cells.
  • Utilized cryo-electron microscopy (EM) for 3D imaging of captured assemblies.
  • Performed computational analysis on the resulting structures.

Main Results:

  • Determined the 3D structure of wild-type BRCA1 engaging the RNA polymerase II (RNAP II) core complex with K63-linked ubiquitin.
  • Identified altered protein interactions and ubiquitination patterns in BRCA1-mutated complexes compared to wild-type.
  • Revealed BRCA1's role in gene regulatory events and its interaction with RNAP II.

Conclusions:

  • Tunable materials and cryo-EM are effective for structural analysis of patient-derived cancer cells.
  • The study expands understanding of BRCA1's function in gene regulation and DNA repair.
  • Findings support the development of new structural oncology applications.