An Mtw1 complex promotes kinetochore biorientation that is monitored by the Ipl1/Aurora protein kinase.
Chromosome segregation depends on kinetochore biorientation so that sister kinetochores attach to microtubules from opposite poles and come under tension. The budding yeast Ipl1/Aurora protein kinase allows the absence of tension to activate the spindle checkpoint. We found that checkpoint activation in the mtw1-1 kinetochore mutant requires Ipl1p, suggesting that Mtw1p promotes tension. We isolated mtw1-1 dosage suppressors and identified Dsn1, a kinetochore protein that immunoprecipitates with the Mif2/CENP-C and Cse4/CENP-A proteins, as well as the Mtw1, Nnf1, and Nsl1 kinetochore proteins. mtw1 and dsn1 mutant strains exhibit similar phenotypes, suggesting that Mtw1p and Dsn1p act together. Although mtw1 mutant cells contained unattached chromosomes, attachment was restored by impairing Ipl1p function. These results suggest that mtw1 mutant kinetochores are competent to bind microtubules but Ipl1p generates unattached chromosomes. We therefore propose that an Mtw1 complex is required for kinetochore biorientation that is monitored by the Ipl1p kinase.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Benjamin A
BA
Pinsky
Sean Y
SY
Tatsutani
Kimberly A
KA
Collins
Sue
S
Biggins
D064127:Aurora Kinases; D001324:Autoantigens; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D018386:Kinetochores / Q000378:metabolism*; D046911:Macromolecular Substances; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism
D001324:Autoantigens; C092746:CSE4 protein, S cerevisiae; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C120362:MTW1 protein, S cerevisiae; D046911:Macromolecular Substances; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D011494:Protein Kinases; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases