@article{32004bdd24bc42928811d24823433a2f,
title = "HAUS, the 8-Subunit Human Augmin Complex, Regulates Centrosome and Spindle Integrity",
abstract = "Background: The assembly of a robust microtubule-based mitotic spindle is a prerequisite for the accurate segregation of chromosomes to progeny. Spindle assembly relies on the concerted action of centrosomes, spindle microtubules, molecular motors, and nonmotor spindle proteins. Results: Here we use an RNA-interference screen of the human centrosome proteome to identify novel regulators of spindle assembly. One such regulator is HAUS, an 8-subunit protein complex that shares homology to Drosophila Augmin. HAUS localizes to interphase centrosomes and to mitotic spindle microtubules, and its disruption induces microtubule-dependent fragmentation of centrosomes along with an increase in centrosome size. HAUS disruption results in the destabilization of kinetochore microtubules and the eventual formation of multipolar spindles. These severe mitotic defects are alleviated by codepletion of NuMA, indicating that both factors regulate opposing activities. HAUS disruption alters NuMA localization, suggesting that mislocalized NuMA activity contributes to the spindle and centrosome defects observed. Conclusion: The human Augmin complex (HAUS) is a critical and evolutionary conserved multisubunit protein complex that regulates centrosome and spindle integrity.",
keywords = "CELLBIO",
author = "Steffen Lawo and Mikhail Bashkurov and Michael Mullin and Ferreria, {Mariana Gomez} and Ralf Kittler and Bianca Habermann and Andrea Tagliaferro and Ina Poser and Hutchins, {James R A} and Bj{\"o}rn Hegemann and Deborah Pinchev and Frank Buchholz and Peters, {Jan Michael} and Hyman, {Anthony A.} and Gingras, {Anne Claude} and Laurence Pelletier",
note = "Funding Information: We would like to thank members of the Pelletier laboratory for stimulating discussions during the course of this work, Mario Sanches for help with chromatography, Andreas Merdes, David Drechsel, and Jeffrey Salisbury for their kind gift of NEDD1, GFP, and Centrin antibodies, and Daniel Durocher, Alex Bird, Christina Yeh, and Friederike Quittnat Pelletier for critical comments on the manuscript. The EU MitoCheck consortium is acknowledged, in particular Karl Mechtler and Martina Sykora at the Vienna mass spectrometry unit and Martina Augsburg at the BAC transgenesis unit in Dresden, for their assistance and sharing of unpublished results. Research in the laboratory of J.-M.P. was supported by Boehringer Ingelheim and the European Commision via MitoCheck. During the course of this work, M.G.F. and R.K. were supported by postdoctoral fellowships from the Fundacion Caja Madrid and the Human Frontier Science Program, respectively. M.M. is supported by an Early Researcher Award to A.-C.G., and A.-C.G. holds the Canada Research Chair in Functional Proteomics and the Lea Reichmann Chair in Cancer Proteomics and is supported by operating grants from the Canadian Institute for Health Research (CIHR MOP-84314). S.L., M.G.F., D.P., and M.B. are supported by operating grants to L.P. from the Natural Science and Engineering Research Council of Canada (RGPIN-355644-2008), National Cancer Institute of Canada (019562), and the HFSP (CDA0044/200). L.P. holds a Canada Research Chair in Centrosome Biogenesis and Function. ",
year = "2009",
month = may,
day = "26",
doi = "10.1016/j.cub.2009.04.033",
language = "English (US)",
volume = "19",
pages = "816--826",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "10",
}