title: Increased Aurora B activity causes continuous disruption of kinetochore-microtubule attachments and spindle instability.
abstract: Aurora B kinase regulates the proper biorientation of sister chromatids during mitosis. Lack of Aurora B kinase function results in the inability to correct erroneous kinetochore-microtubule attachments and gives rise to aneuploidy. Interestingly, increased Aurora B activity also leads to problems with chromosome segregation, and overexpression of this kinase has been observed in various types of cancer. However, little is known about the mechanisms by which an increase in Aurora B kinase activity can impair mitotic progression and cell viability. Here, using a yeast model, we demonstrate that increased Aurora B activity as a result of the overexpression of the Aurora B and inner centromere protein homologs triggers defects in chromosome segregation by promoting the continuous disruption of chromosome-microtubule attachments even when sister chromatids are correctly bioriented. This disruption leads to a constitutive activation of the spindle-assembly checkpoint, which therefore causes a lack of cytokinesis even though spindle elongation and chromosome segregation take place. Finally, we demonstrate that this increase in Aurora B activity causes premature collapse of the mitotic spindle by promoting instability of the spindle midzone.
authors.affiliation: Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), 41092 Seville, Spain; Spanish National Research Council, 41092 Seville, Spain; and.
authors.forename: Marta
authors.initials: M
authors.lastname: Muñoz-Barrera
authors.affiliation: Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), 41092 Seville, Spain; Department of Genetics, University of Seville, 41092 Seville, Spain fernando.monje@cabimer.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Monje-Casas
mesh_terms: D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000201:enzymology / Q000235:genetics; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000201:enzymology*; D008870:Microtubules / Q000201:enzymology* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000201:enzymology* / Q000235:genetics
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D064107:Aurora Kinase B
keywords: CPC; INCENP; Ipl1; SAC; Sli15