Spindle checkpoint proteins and chromosome-microtubule attachment in budding yeast.
Accurate chromosome segregation depends on precise regulation of mitosis by the spindle checkpoint. This checkpoint monitors the status of kinetochore-microtubule attachment and delays the metaphase to anaphase transition until all kinetochores have formed stable bipolar connections to the mitotic spindle. Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1-3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3. In animal cells, all known spindle checkpoint proteins are recruited to kinetochores during normal mitoses. In contrast, we show that whereas Saccharomyces cerevisiae Bub1p and Bub3p are bound to kinetochores early in mitosis as part of the normal cell cycle, Mad1p and Mad2p are kinetochore bound only in the presence of spindle damage or kinetochore lesions that interfere with chromosome-microtubule attachment. Moreover, although Mad1p and Mad2p perform essential mitotic functions during every division cycle in mammalian cells, they are required in budding yeast only when mitosis goes awry. We propose that differences in the behavior of spindle checkpoint proteins in animal cells and budding yeast result primarily from evolutionary divergence in spindle assembly pathways.
Gillett
Emily S
ES
Massachusetts Institute of Technology, Department of Biology, 77 Massachusetts Ave., 68-371 Cambridge, MA 02139, USA.
Espelin
Christopher W
CW
Sorger
Peter K
PK
D000818:Animals; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000378:metabolism*; D018816:Genes, cdc; D047908:Intracellular Signaling Peptides and Proteins; D018386:Kinetochores / Q000378:metabolism; D046911:Macromolecular Substances; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism*
C070351:BUB2 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C116003:DAM1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; C501382:MAD1 protein, S cerevisiae; C577695:MAD2 protein, S cerevisiae; D046911:Macromolecular Substances; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C109414:STU2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D064127:Aurora Kinases; C090464:Bub1 spindle checkpoint protein; C576961:IPL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases