A Bub2p-dependent spindle checkpoint pathway regulates the Dbf2p kinase in budding yeast.
Exit from mitosis in all eukaroytes requires inactivation of the mitotic kinase. This occurs principally by ubiquitin-mediated proteolysis of the cyclin subunit controlled by the anaphase-promoting complex (APC). However, an abnormal spindle and/or unattached kinetochores activates a conserved spindle checkpoint that blocks APC function. This leads to high mitotic kinase activity and prevents mitotic exit. DBF2 belongs to a group of budding yeast cell cycle genes that when mutated prevent cyclin degradation and block exit from mitosis. DBF2 encodes a protein kinase which is cell cycle regulated, peaking in metaphase-anaphase B/telophase, but its function remains unknown. Here, we show the Dbf2p kinase activity to be a target of the spindle checkpoint. It is controlled specifically by Bub2p, one of the checkpoint components that is conserved in fission yeast and higher eukaroytic cells. Significantly, in budding yeast, Bub2p shows few genetic or biochemical interactions with other members of the spindle checkpoint. Our data now point to the protein kinase Mps1p triggering a new parallel branch of the spindle checkpoint in which Bub2p blocks Dbf2p function.
Fesquet
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Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Fitzpatrick
P J
PJ
Johnson
A L
AL
Kramer
K M
KM
Toyn
J H
JH
Johnston
L H
LH
D000705:Anaphase; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D004789:Enzyme Activation; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D064246:Mad2 Proteins; D008677:Metaphase; D008954:Models, Biological; D009687:Nuclear Proteins; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus
C070351:BUB2 protein, S cerevisiae; C513239:CEF1 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C085768:DBF2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C093416:MPS1 protein, S cerevisiae