title: Chromosome segregation in fission yeast with mutations in the tubulin folding cofactor D.
abstract: Faithful chromosome segregation requires the combined activities of the microtubule-based mitotic spindle and the multiple proteins that form mitotic kinetochores. Here, we show that the fission yeast mitotic mutant, tsm1-512, is an allele of the tubulin folding chaperone, cofactor D. Chromosome segregation in this and in an additional cofactor D mutant depends on growth conditions that are monitored specifically by the mitotic checkpoint proteins Mad1, 2, 3 and Bub3. The temperature-sensitive mutants we have used disrupt the function of cofactor D to different extents, but both strains form a mitotic spindle in which the poles separate in anaphase. However, chromosome segregation is often unequal, apparently due to a defect in kinetochore-microtubule interactions. Mutations in cofactor D render cells particularly sensitive to the expression levels of a CENP-B-like protein, Abp1p, which works as an allele-specific, high-copy suppressor of cofactor D. This and other genetic interactions between cofactor D mutants and specific kinetochore and spindle components suggest their critical role in establishing the normal kinetochore-microtubule interface.
authors.affiliation: National Research Center for Hematology, Moscow, Russia.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Fedyanina
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Mardanov
authors.forename: Ekaterina M
authors.initials: EM
authors.lastname: Tokareva
authors.forename: J Richard
authors.initials: JR
authors.lastname: McIntosh
authors.forename: Ekaterina L
authors.initials: EL
authors.lastname: Grishchuk
mesh_terms: D000483:Alleles; D020090:Chromosome Segregation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C110653:Alp1 protein, S pombe; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; C097691:cbp1 protein, S pombe