title: Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1.
abstract: Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Friederike
authors.initials: F
authors.lastname: Althoff
authors.forename: Roger E
authors.initials: RE
authors.lastname: Karess
authors.forename: Christian F
authors.initials: CF
authors.lastname: Lehner
mesh_terms: D000705:Anaphase; D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D018386:Kinetochores / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D064246:Mad2 Proteins; D008677:Metaphase; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D064246:Mad2 Proteins; D017346:Protein Serine-Threonine Kinases; D000097573:Red Fluorescent Protein; C501876:Mps1 protein, Drosophila