MAD3 Encodes a Novel Component of the Spindle Checkpoint which Interacts with Bub3p, Cdc20p, and Mad2p

doi:10.1083/jcb.148.5.871

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© The Rockefeller University Press, 0021-9525/2000/3/871/ $5.00
The Journal of Cell Biology, Volume 148, Number 5, March 6, 2000 871-882

Original Article

MAD3 Encodes a Novel Component of the Spindle Checkpoint which Interacts with Bub3p, Cdc20p, and Mad2p

Kevin G. Hardwick^a, Raymond C. Johnston^a, Dana L. Smith^b, and Andrew W. Murray^b
^a Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom
^b Department of Physiology, University of California, San Francisco, California 94143

Correspondence to: Kevin G. Hardwick, Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, United Kingdom. Tel:44 131 650 7091 Fax:44 131 650 7037 E-mail:hardwick{at}holyrood.ed.ac.uk.

We show that MAD3 encodes a novel 58-kD nuclear protein whichis not essential for viability, but is an integral componentof the spindle checkpoint in budding yeast. Sequence analysisreveals two regions of Mad3p that are 46 and 47% identical tosequences in the NH₂-terminal region of the budding yeast Bub1protein kinase. Bub1p is known to bind Bub3p (Roberts et al.1994 ) and we use two-hybrid assays and coimmunoprecipitationexperiments to show that Mad3p can also bind to Bub3p. In addition,we find that Mad3p interacts with Mad2p and the cell cycle regulatorCdc20p. We show that the two regions of homology between Mad3pand Bub1p are crucial for these interactions and identify lossof function mutations within each domain of Mad3p. We discussroles for Mad3p and its interactions with other spindle checkpointproteins and with Cdc20p, the target of the checkpoint.

Key Words: MAD3, checkpoint, BUB3, CDC20, MAD2

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