title: GAS2L3, a target gene of the DREAM complex, is required for proper cytokinesis and genomic stability.
abstract: The mammalian DREAM complex is a key regulator of cell-cycle-regulated gene transcription and drives the expression of many gene products required for mitosis and cytokinesis. In this study, we characterized GAS2L3, which belongs to the GAS2 family of proteins with putative actin- and microtubule-binding domains as a target gene of DREAM. We found that GAS2L3 localizes to the spindle midzone and the midbody during anaphase and cytokinesis, respectively. Biochemical studies show that GAS2L3 binds to and bundles microtubules as well as F-actin in vitro. Strikingly, the RNAi-mediated knockdown of GAS2L3 results in chromosome segregation defects in multinucleated cells and in cells with multi-lobed nuclei. Likewise, chronic downregulation of GAS2L3 causes chromosome loss and aneuploidy. Time-lapse videomicroscopy experiments in GAS2L3-knockdown cells reveal abnormal oscillation of chromatin and the spindle during cytokinesis. Taken together, our data reveal novel, important roles of GAS2L3 for faithful cell division. Our work thus contributes to the understanding of how DREAM regulates cytokinesis.
authors.affiliation: Biozentrum, Universität Würzburg, Würzburg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wolter
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schmitt
authors.forename: Marc
authors.initials: M
authors.lastname: Fackler
authors.forename: Heidi
authors.initials: H
authors.lastname: Kremling
authors.forename: Leona
authors.initials: L
authors.lastname: Probst
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hauser
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Gruss
authors.forename: Stefan
authors.initials: S
authors.lastname: Gaubatz
mesh_terms: D048749:Cytokinesis; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: D051605:Kv Channel-Interacting Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; C569298:GAS2L3 protein, human; C496749:KCNIP3 protein, human