Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption

• Published in: Science (American Association for the Advancement of Science) Vol. 273; no. 5277; pp. 953 - 956
• Main Authors: Hardwick, K.G. (University of California, San Francisco, CA.), Weiss, E, Luca, F.C, Winey, M, Murray, A.W
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 16.08.1996; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Biological and medical sciences; Cancer; Carrier Proteins; Cell Cycle; Cell Cycle Proteins; Cell growth; Cell regulation; Cellular biology; Cellular control mechanisms; Cellular immunity; Chemotherapy; Classical genetics, quantitative genetics, hybrids; DNA; DOSAGE BIOLOGIQUE; Duplication; ENSAYO BIOLOGICO; EXPERIMENTACION IN VITRO; EXPERIMENTATION IN VITRO; EXPRESION GENICA; EXPRESSION DES GENES; FOSFORILACION; Fundamental and applied biological sciences. Psychology; Fungal Proteins - metabolism; Genetics; Genetics of eukaryotes. Biological and molecular evolution; LEVADURA; LEVURE; MITOSE; MITOSIS; Mitotic spindle apparatus; Mutation; Nuclear Proteins - metabolism; Phosphoproteins - metabolism; PHOSPHORYLATION; Poly-ADP-Ribose Binding Proteins; Protein Kinases; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; PROTEINAS; PROTEINE; Recombinant Fusion Proteins - metabolism; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Saccharomycetales; Spindle (Cell division); Spindle (Cytoplasm); Spindle Apparatus - metabolism; Spindle pole body; Thallophyta, bryophyta; Vegetals; Yeast; Yeasts; Phosphorylation; Yeast; Enzyme; Segregation; Transferases; Chromosome; Mitotic spindle; Fungi; Disjunction; Gene; Protein kinase; Cell cycle; Ascomycetes; Mutation; Saccharomyces cerevisiae; Thallophyta
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.273.5277.953

The spindle assembly checkpoint keeps cells with defective spindles from initiating chromosome segregation. The protein kinase Mps1 phosphorylates the yeast protein Mad1p when this checkpoint is activated, and the overexpression of Mps1p induces modification of Mad1p and arrests wild-type yeast cells in mitosis with morphologically normal spindles. Spindle assembly checkpoint mutants overexpressing Mps1p pass through mitosis without delay and can produce viable progeny, which demonstrates that the arrest of wild-type cells results from inappropriate activation of the checkpoint in cells whose spindle is fully functional. Ectopic activation of cell-cycle checkpoints might be used to exploit the differences in checkpoint status between normal and tumor cells and thus improve the selectivity of chemotherapy