Lesions in Many Different Spindle Components Activate the Spindle Checkpoint in the Budding Yeast Saccharomyces cerevisiae

Corresponding author: Andrew W. Murray, Physiology Box 0444, UCSF, Parnassus Ave., San Francisco, CA 94143-0444., amurray{at}socrates.ucsf.edu (E-mail)

Communicating editor: D. BOTSTEIN

The spindle checkpoint arrests cells in mitosis in response to defects in the assembly of the mitotic spindle or errors in chromosome alignment. We determined which spindle defects the checkpoint can detect by examining the interaction of mutations that compromise the checkpoint (mad1, mad2, and mad3) with those that damage various structural components of the spindle. Defects in microtubule polymerization, spindle pole body duplication, microtubule motors, and kinetochore components all activate the MAD-dependent checkpoint. In contrast, the cell cycle arrest caused by mutations that induce DNA damage (cdc13), inactivate the cyclin proteolysis machinery (cdc16 and cdc23), or arrest cells in anaphase (cdc15) is independent of the spindle checkpoint.

This article has been cited by other articles:

				Y.-H. Chi, K. Haller, M. D. Ward, O. J. Semmes, Y. Li, and K.-T. Jeang Requirements for Protein Phosphorylation and the Kinase Activity of Polo-like Kinase 1 (Plk1) for the Kinetochore Function of Mitotic Arrest Deficiency Protein 1 (Mad1) J. Biol. Chem., December 19, 2008; 283(51): 35834 - 35844. [Abstract] [Full Text] [PDF]

				M. Tarailo, S. Tarailo, and A. M. Rose Synthetic Lethal Interactions Identify Phenotypic "Interologs" of the Spindle Assembly Checkpoint Components Genetics, December 1, 2007; 177(4): 2525 - 2530. [Abstract] [Full Text] [PDF]

				C. A. Eckert, D. J. Gravdahl, and P. C. Megee The enhancement of pericentromeric cohesin association by conserved kinetochore components promotes high-fidelity chromosome segregation and is sensitive to microtubule-based tension Genes & Dev., February 1, 2007; 21(3): 278 - 291. [Abstract] [Full Text] [PDF]

				C. Clemenson and M.-C. Marsolier-Kergoat The Spindle Assembly Checkpoint Regulates the Phosphorylation State of a Subset of DNA Checkpoint Proteins in Saccharomyces cerevisiae Mol. Cell. Biol., December 15, 2006; 26(24): 9149 - 9161. [Abstract] [Full Text] [PDF]

				A. Poddar, P. T. Stukenberg, and D. J. Burke Two Complexes of Spindle Checkpoint Proteins Containing Cdc20 and Mad2 Assemble during Mitosis Independently of the Kinetochore in Saccharomyces cerevisiae Eukaryot. Cell, May 1, 2005; 4(5): 867 - 878. [Abstract] [Full Text] [PDF]

				M. S. Lee and F. A. Spencer Bipolar orientation of chromosomes in Saccharomyces cerevisiae is monitored by Mad1 and Mad2, but not by Mad3 PNAS, July 20, 2004; 101(29): 10655 - 10660. [Abstract] [Full Text] [PDF]

				E. Trelles-Sticken, J. Loidl, and H. Scherthan Increased ploidy and KAR3 and SIR3 disruption alter the dynamics of meiotic chromosomes and telomeres J. Cell Sci., June 15, 2003; 116(12): 2431 - 2442. [Abstract] [Full Text] [PDF]

				O. Dahan and M. Kupiec Mutations in genes of Saccharomyces cerevisiae encoding pre-mRNA splicing factors cause cell cycle arrest through activation of the spindle checkpoint Nucleic Acids Res., October 15, 2002; 30(20): 4361 - 4370. [Abstract] [Full Text] [PDF]

				C. D. Warren, D. M. Brady, R. C. Johnston, J. S. Hanna, K. G. Hardwick, and F. A. Spencer Distinct Chromosome Segregation Roles for Spindle Checkpoint Proteins Mol. Biol. Cell, September 1, 2002; 13(9): 3029 - 3041. [Abstract] [Full Text] [PDF]

				P. M. Garber and J. Rine Overlapping Roles of the Spindle Assembly and DNA Damage Checkpoints in the Cell-Cycle Response to Altered Chromosomes in Saccharomyces cerevisiae Genetics, June 1, 2002; 161(2): 521 - 534. [Abstract] [Full Text] [PDF]

				R. M. Q. Shanks, R. J. Kamieniecki, and D. S. Dawson The Kar3-Interacting Protein Cik1p Plays a Critical Role in Passage Through Meiosis I in Saccharomyces cerevisiae Genetics, November 1, 2001; 159(3): 939 - 951. [Abstract] [Full Text] [PDF]

				R. D. Gardner, A. Poddar, C. Yellman, P. A. Tavormina, M. C. Monteagudo, and D. J. Burke The Spindle Checkpoint of the Yeast Saccharomyces cerevisiae Requires Kinetochore Function and Maps to the CBF3 Domain Genetics, April 1, 2001; 157(4): 1493 - 1502. [Abstract] [Full Text]

				I. M. Cheeseman, M. Enquist-Newman, T. Muller-Reichert, D. G. Drubin, and G. Barnes Mitotic Spindle Integrity and Kinetochore Function Linked by the Duo1p/Dam1p Complex J. Cell Biol., January 8, 2001; 152(1): 197 - 212. [Abstract] [Full Text] [PDF]

				R. Krishnan, F. Pangilinan, C. Lee, and F. Spencer Saccharomyces cerevisiae BUB2 Prevents Mitotic Exit in Response to Both Spindle and Kinetochore Damage Genetics, October 1, 2000; 156(2): 489 - 500. [Abstract] [Full Text]

				A. D. Rudner, K. G. Hardwick, and A. W. Murray Cdc28 Activates Exit from Mitosis in Budding Yeast J. Cell Biol., June 26, 2000; 149(7): 1361 - 1376. [Abstract] [Full Text] [PDF]

				J. L. Paluh, E. Nogales, B. R. Oakley, K. McDonald, A. L. Pidoux, and W. Z. Cande A Mutation in gamma -Tubulin Alters Microtubule Dynamics and Organization and Is Synthetically Lethal with the Kinesin-like Protein Pkl1p Mol. Biol. Cell, April 1, 2000; 11(4): 1225 - 1239. [Abstract] [Full Text]

				T. Furuta, S. Tuck, J. Kirchner, B. Koch, R. Auty, R. Kitagawa, A. M. Rose, and D. Greenstein EMB-30: An APC4 Homologue Required for Metaphase-to-Anaphase Transitions during Meiosis and Mitosis in Caenorhabditis elegans Mol. Biol. Cell, April 1, 2000; 11(4): 1401 - 1419. [Abstract] [Full Text]

				K. G. Hardwick, R. C. Johnston, D. L. Smith, and A. W. Murray MAD3 Encodes a Novel Component of the Spindle Checkpoint which Interacts with Bub3p, Cdc20p, and Mad2p J. Cell Biol., March 6, 2000; 148(5): 871 - 882. [Abstract] [Full Text] [PDF]

				Y. Murakumo, T. Roth, H. Ishii, D. Rasio, S.-i. Numata, C. M. Croce, and R. Fishel A Human REV7 Homolog That Interacts with the Polymerase zeta Catalytic Subunit hREV3 and the Spindle Assembly Checkpoint Protein hMAD2 J. Biol. Chem., February 11, 2000; 275(6): 4391 - 4397. [Abstract] [Full Text] [PDF]