title: Chromosome Missegregation Associated with RUVBL1 Deficiency.
abstract: RUVBL1 (RuvB-like1) and RUVBL2 (RuvB-like 2) are integral components of multisubunit protein complexes involved in processes ranging from cellular metabolism, transcription and chromatin remodeling to DNA repair. Here, we show that although RUVBL1 and RUVBL2 are known to form heterodimeric complexes in which they stabilize each other, the subunits separate during cytokinesis. In anaphase-to-telophase transition, RUVBL1 localizes to structures of the mitotic spindle apparatus, where it partially co-localizes with polo-like kinase 1 (PLK1). The ability of PLK1 to phosphorylate RUVBL1-but not RUVBL2-in vitro and their physical association in vivo suggest that this kinase differentially regulates the function of the RuvB-like proteins during mitosis. We further show that siRNA-mediated knock-down of RuvB-like proteins causes severe defects in chromosome alignment and segregation. In addition, we show that the ATPase activity of RUVBL1 is indispensable for cell proliferation. Our data thus demonstrate that RUVBL1 is essential for efficient mitosis and proliferation.
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Gentili
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Dennis
authors.initials: D
authors.lastname: Castor
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Svenja
authors.initials: S
authors.lastname: Kaden
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Lauterbach
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Gysi
authors.affiliation: Institute of Biochemistry, Schafmattstrasse 18, HPM E17.2, Swiss Institute of Technology Zurich (ETHZ), CH-8093, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Steigemann
authors.affiliation: Institute of Biochemistry, Schafmattstrasse 18, HPM E17.2, Swiss Institute of Technology Zurich (ETHZ), CH-8093, Zurich, Switzerland.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Gerlich
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
authors.affiliation: Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D048749:Cytokinesis / Q000502:physiology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004265:DNA Helicases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C486549:RUVBL1 protein, human; C122079:RUVBL2 protein, human