Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption.
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.
Hardwick
K G
KG
Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
Weiss
E
E
Luca
F C
FC
Winey
M
M
Murray
A W
AW
D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000378:metabolism*
C070352:BUB3 protein, S cerevisiae; C489444:BUB3 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C501382:MAD1 protein, S cerevisiae; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human; C093416:MPS1 protein, S cerevisiae