High-content screening and profiling of drug activity in an automated centrosome-duplication assa

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2005
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Perlman, Zachary E.
Mitchison, Timothy J.
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ChemBioChem. 2005, 6(1), pp. 145-151. ISSN 1439-4227. Available under: doi: 10.1002/cbic.200400266
Zusammenfassung

Maintenance of centrosome number is essential for cell-cycle progression and genomic stability, but investigation of this regulation has been limited by assay difficulty. We present a fully automated image-based centrosome-duplication assay that is accurate and robust enough for both careful cell-biology studies and high-throughput screening, and employ this assay in a series of chemical-genetic studies. We observe that a simple cytometric profiling strategy, which is based on organelle size, groups compounds with similar mechanisms of action; this suggests a simple strategy for excluding compounds that undesirably target such activities as protein synthesis and microtubule dynamics. Screening a library of compounds of known activity, we found unexpected effects on centrosome duplication by a number of drugs, most notably isoform-specific protein kinase C inhibitors and retinoic acid receptor agonists. From a 16 320-member library of uncharacterized small molecules, we identified five potent centrosome-duplication inhibitors that do not target microtubule dynamics or protein synthesis. The analysis methodology reported here is directly relevant to studies of centrosome regulation in a variety of systems and is adaptable to a wide range of other biological problems.

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570 Biowissenschaften, Biologie
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Small Molecule, Chemical Biology, Mitose, Chromosomenbande, Zellteilung, Mikrotubuli Kinesin, bioinformatics, biological information, centrosomes, drugs, high-throughput screening
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ISO 690PERLMAN, Zachary E., Timothy J. MITCHISON, Thomas U. MAYER, 2005. High-content screening and profiling of drug activity in an automated centrosome-duplication assa. In: ChemBioChem. 2005, 6(1), pp. 145-151. ISSN 1439-4227. Available under: doi: 10.1002/cbic.200400266
BibTex
@article{Perlman2005-01Highc-14049,
  year={2005},
  doi={10.1002/cbic.200400266},
  title={High-content screening and profiling of drug activity in an automated centrosome-duplication assa},
  number={1},
  volume={6},
  issn={1439-4227},
  journal={ChemBioChem},
  pages={145--151},
  author={Perlman, Zachary E. and Mitchison, Timothy J. and Mayer, Thomas U.}
}
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