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Mol Cell Biol, May 1998, p. 2738-2747, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Bub1p Kinase Activates the Saccharomyces
cerevisiae Spindle Assembly Checkpoint
Katie A.
Farr and
M. Andrew
Hoyt*
Department of Biology, The Johns Hopkins
University, Baltimore, Maryland 21218
Received 10 December 1997/Returned for modification 26 January
1998/Accepted 23 February 1998
Saccharomyces cerevisiae BUB1 encodes a protein kinase
required for spindle assembly checkpoint function. In the presence of
spindle damage, BUB1 is required to prevent cell cycle
progression into anaphase. We have identified a dominantly acting
BUB1 allele that appears to activate the spindle assembly
checkpoint pathway in cells with undamaged spindles. High-level
expression of BUB1-5 did not cause detectable spindle
damage, yet it delayed yeast cells in mitosis at a stage following
bipolar spindle assembly but prior to anaphase spindle elongation.
Delayed cells possessed a G2 DNA content and elevated Clb2p
mitotic cyclin levels. Unlike cells delayed in mitosis by spindle
damage or MPS1 kinase overexpression, hyperphosphorylated
forms of the Mad1p checkpoint protein did not accumulate. Similar to
cells overexpressing MPS1, the BUB1-5 delay was
dependent upon the functions of the other checkpoint genes, including
BUB2 and BUB3 and MAD1,
MAD2, and MAD3. We found that the mitotic delay
caused by BUB1-5 or MPS1 overexpression was
interdependent upon the function of the other. This suggests that the
Bub1p and Mps1p kinases act together at an early step in generating the
spindle damage signal.
*
Corresponding author. Mailing address: Department of
Biology, The Johns Hopkins University, Baltimore, MD 21218. Phone:
(410) 516-7299. Fax: (410) 516-5213. E-mail: hoyt{at}jhu.edu.
Mol Cell Biol, May 1998, p. 2738-2747, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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