Systematic Analysis of Human Protein Complexes Identifies Chromosome Segregation Proteins

James R. A. Hutchins(Research Institute of Molecular Pathology), Yusuke Toyoda(Max Planck Institute of Molecular Cell Biology and Genetics), Björn Hegemann(Research Institute of Molecular Pathology), Ina Poser(Max Planck Institute of Molecular Cell Biology and Genetics), Jean-Karim Hèriché(Max Planck Society), Martina M. Sykora(Research Institute of Molecular Pathology), Martina Augsburg(Max Planck Institute of Molecular Cell Biology and Genetics), Otto Hudecz(Research Institute of Molecular Pathology), Bettina A. Buschhorn(Research Institute of Molecular Pathology), Jutta Bulkescher(European Molecular Biology Laboratory), Christian Conrad(European Molecular Biology Laboratory), David Comartin(Mount Sinai Hospital), Alexander Schleiffer(Research Institute of Molecular Pathology), Mihail Sarov(Max Planck Institute of Molecular Cell Biology and Genetics), Andrei Pozniakovsky(Max Planck Institute of Molecular Cell Biology and Genetics), Mikołaj Słabicki(Max Planck Institute of Molecular Cell Biology and Genetics), Siegfried Schloissnig(German Cancer Research Center), Ines Steinmacher(Research Institute of Molecular Pathology), Marit Leuschner(Max Planck Institute of Molecular Cell Biology and Genetics), Andrea Ssykor(Max Planck Institute of Molecular Cell Biology and Genetics), Steffen Lawo(Mount Sinai Hospital), Laurence Pelletier(Mount Sinai Hospital), Holger Stark(Max Planck Society), Kim Nasmyth(Research Institute of Molecular Pathology), Jan Ellenberg(European Molecular Biology Laboratory), Richard Durbin(Wellcome Sanger Institute), Frank Buchholz(Max Planck Institute of Molecular Cell Biology and Genetics), Karl Mechtler(Research Institute of Molecular Pathology), Anthony A. Hyman(Max Planck Institute of Molecular Cell Biology and Genetics), Jan‐Michael Peters(Max Planck Society)
Science
April 1, 2010
10.1126/science.1181348
Cited by 505Open Access
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Abstract

Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood. Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes, many of which had not or had only incompletely been characterized. This work has led to the discovery of previously unknown, evolutionarily conserved subunits of the anaphase-promoting complex and the gamma-tubulin ring complex--large complexes that are essential for spindle assembly and chromosome segregation. The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells.

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