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Vol. 10, Issue 8, 2607-2618, August 1999
*Department of Physiology, University of California, San Francisco,
San Francisco, California 94143-0444; The spindle checkpoint arrests the cell cycle at metaphase in the
presence of defects in the mitotic spindle or in the attachment of
chromosomes to the spindle. When spindle assembly is disrupted, the
budding yeast mad and bub mutants fail to arrest
and rapidly lose viability. We have cloned the MAD2 gene,
which encodes a protein of 196 amino acids that remains at a constant
level during the cell cycle. Gel filtration and co-immunoprecipitation
analyses reveal that Mad2p tightly associates with another spindle
checkpoint component, Mad1p. This association is independent of cell
cycle stage and the presence or absence of other known checkpoint
proteins. In addition, Mad2p binds to all of the different
phosphorylated isoforms of Mad1p that can be resolved on SDS-PAGE.
Deletion and mutational analysis of both proteins indicate that
association of Mad2p with Mad1p is critical for checkpoint function and
for hyperphosphorylation of Mad1p.
Department of
Molecular Biology and Genetics, Cornell University, Ithaca, New York
14853; and §Institute of Cell and Molecular Biology,
University of Edinburgh, Edinburgh, EH9 3JR, United Kingdom
Corresponding author. E-mail address:
rc70{at}cornell.edu.
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