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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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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

@article{Perlman2005-01High--14049, title={High-content screening and profiling of drug activity in an automated centrosome-duplication assa}, year={2005}, doi={10.1002/cbic.200400266}, number={1}, volume={6}, issn={1439-4227}, journal={ChemBioChem}, pages={145--151}, author={Perlman, Zachary E. and Mitchison, Timothy J. and Mayer, Thomas U.} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/14049"> <dc:language>eng</dc:language> <dc:creator>Mitchison, Timothy J.</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/14049"/> <dc:contributor>Perlman, Zachary E.</dc:contributor> <dc:creator>Mayer, Thomas U.</dc:creator> <dcterms:title>High-content screening and profiling of drug activity in an automated centrosome-duplication assa</dcterms:title> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dcterms:abstract xml:lang="eng">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.</dcterms:abstract> <dcterms:issued>2005-01</dcterms:issued> <dc:contributor>Mayer, Thomas U.</dc:contributor> <dc:contributor>Mitchison, Timothy J.</dc:contributor> <dc:creator>Perlman, Zachary E.</dc:creator> <dc:rights>deposit-license</dc:rights> <dcterms:bibliographicCitation>Publ. in: Chembiochem ; 6 (2005), 1. - S. 145-151</dcterms:bibliographicCitation> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-01-11T09:44:06Z</dcterms:available> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-01-11T09:44:06Z</dc:date> </rdf:Description> </rdf:RDF>

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