High-content screening and profiling of drug activity in an automated centrosome-duplication assa
High-content screening and profiling of drug activity in an automated centrosome-duplication assa
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2005
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ChemBioChem ; 6 (2005), 1. - pp. 145-151. - ISSN 1439-4227
Abstract
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 Biosciences, Biology
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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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PERLMAN, 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. 6(1), pp. 145-151. ISSN 1439-4227. Available under: doi: 10.1002/cbic.200400266BibTex
@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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