GAS2L3, a novel target gene of the dream complex, is required for proper cytokinesis and genomic stability

• DOI: 10.1242/jcs.097253
• Publication Date: 2012-02-18T01:57:33Z
• Authors: Patrick Wolter; Kathrin Schmitt; Marc Fackler; Heidi Kremling; Leona Probst; Stefanie Hauser; Oliver J. Gruss; Stefan Gaubatz
• Keywords: 0301 basic medicine; Microfilament Proteins; Kv Channel-Interacting Proteins; Spindle Apparatus; Microtubules; Genomic Instability; Repressor Proteins; Protein Transport; 03 medical and health sciences; Humans; Microtubule-Associated Proteins; Cytokinesis; HeLa Cells; Protein Binding

The mammalian DREAM complex is 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 a novel target gene of DREAM, GAS2L3, which belongs to the GAS2 family of proteins with putative actin and microtubule binding domains. 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 knock-down of GAS2L3 results in chromosome segregation defects, in multinucleated cells and cells with multi-lobed nuclei. Likewise, chronic downregulation of GAS2L3 causes chromosome loss and aneuploidy. Time-lapse video microscopy experiments in GAS2L3 knock-down 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.