title: A Bir1-Sli15 complex connects centromeres to microtubules and is required to sense kinetochore tension.
abstract: Proper connections between centromeres and spindle microtubules are of critical importance in ensuring accurate segregation of the genome during cell division. Using an in vitro approach based on the sequence-specific budding yeast centromere, we identified a complex of the chromosomal passenger proteins Bir1 and Sli15 (Survivin and INCENP) that links centromeres to microtubules. This linkage does not require Ipl1/Aurora B kinase, whose targeting and activation are controlled by Bir1 and Sli15. Ipl1 is the tension-dependent regulator of centromere-microtubule interactions that ensures chromosome biorientation on the spindle. Elimination of the linkage between centromeres and microtubules mediated by Bir1-Sli15 phenocopies mutations that selectively cripple Ipl1 kinase activation. These findings lead us to propose that the Bir1-Sli15-mediated linkage, which bridges centromeres and microtubules and includes the Aurora kinase-activating domain of INCENP family proteins, is the tension sensor that relays the mechanical state of centromere-microtubule attachments into local control of Ipl1 kinase activity.
authors.affiliation: Ludwig Institute for Cancer Research/Department of Cellular and Molecular Medicine, CMM-E Room 3052, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Sharsti
authors.initials: S
authors.lastname: Sandall
authors.forename: Fedor
authors.initials: F
authors.lastname: Severin
authors.forename: Ian X
authors.initials: IX
authors.lastname: McLeod
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
authors.forename: Anthony
authors.initials: A
authors.lastname: Hyman
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
mesh_terms: D064127:Aurora Kinases; D002453:Cell Cycle; D002503:Centromere / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C506586:CBF3b protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C480084:Sli15 protein, S cerevisiae; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases