title: Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
abstract: The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.
authors.affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Blower
authors.forename: Tanya
authors.initials: T
authors.lastname: Daigle
authors.forename: Thom
authors.initials: T
authors.lastname: Kaufman
authors.forename: Gary H
authors.initials: GH
authors.lastname: Karpen
mesh_terms: D000483:Alleles; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D000076247:Centromere Protein A; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D006579:Heterozygote; D006657:Histones / Q000235:genetics*; D018386:Kinetochores / Q000378:metabolism*; D008938:Mitosis; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D008941:Spindle Apparatus
chemical_list: C506005:BubR1 protein, Drosophila; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; C427237:Cid protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones