Abstract
Checkpoint controls ensure that events of the cell-division cycle are completed with fidelity and in the correct order. In budding yeast with a mutation in the motor protein dynein, the mitotic spindle is often misaligned and therefore slow to enter the neck between mother cell and budding daughter cell. When this occurs, cytokinesis (division of the cytoplasm into two) is delayed until the spindle is properly positioned1. Here we describe mutations that abolish this delay, indicating the existence of a new checkpoint mechanism. One mutation lies in the gene encoding the yeast homologue of EB1, a human protein that binds the adenomatous polyposis coli (APC) protein, a tumour suppressor. EB1 is located on microtubules of the mitotic spindle and is important in spindle assembly. EB1 may therefore, by associating with microtubules, contribute to the sensor mechanism that activates the checkpoint. Another mutation affects Stt4, a phosphatidylinositol-4-OH kinase. Cold temperature is an environmental stimulus that causes misalignment of the mitotic spindle in yeast and appears to activate this checkpoint mechanism.
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References
Yeh, E. et al. Spindle dynamics and cell cycle regulation of dynein in the budding yeast, Saccharomyces cerevisiae. J. Cell Biol. 130, 687–700 (1995).
Muhua, L., Karpova, T. S. & Cooper, J. A. Ayeast actin-related protein homologous to that in vertebrate dynactin complex is important for spindle orientation and nuclear migration. Cell 78, 669–679 (1994).
McMillan, J. N. & Tatchell, K. The JNM1 gene in the yeast Saccharomyces cerevisiae is required for nuclear migration and spindle orientation during the mitotic cell cycle. J. Cell Biol. 125, 143–158 (1994).
Yoshida, S. et al. Anovel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae. J. Biol. Chem. 269, 1166–1172 (1994).
Su, L. K. et al. APC binds to the novel protein EB1. Cancer Res. 55, 2972–2977 (1995).
Kinzler, K. W. & Vogelstein, B. Lessons from hereditary colorectal cancer. Cell 87, 159–170 (1996).
Hartwell, L. H. & Weinert, T. A. Checkpoints: controls that ensure the order of cell cycle events. Science 246, 629–634 (1989).
Elledge, S. J. Cell cycle checkpoints: preventing an identity crisis. Science 274, 1664–1672 (1996).
Murray, A. W. The genetics of cell cycle checkpoints. Curr. Opin. Genet. Dev. 5, 5–11 (1995).
Munemitsu, S. et al. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 54, 3676–3681 (1994).
Smith, K. J. et al. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 54, 3672–3675 (1994).
Beinhauer, J. D. et al. Mal3, the fission yeast homologue of the human APC-interacting protein EB-1 is required for microtubule integrity and the maintenance of cell form. J. Cell Biol. 139, 717–728 (1997).
Schwartz, K., Richards, K. & Botstein, D. BIM1 encodes a microtubule-binding protein in yeast. Mol. Biol. Cell 8, 2677–2691 (1997).
Sullivan, D. S. & Huffaker, T. C. Astral microtubules are not required for anaphase B in Saccharomyces cerevisiae. J. Cell Biol. 119, 379–388 (1992).
Li, Y. Y. et al. Disruption of mitotic spindle orientation in a yeast dynein mutant. Proc. Natl Acad. Sci. USA 90, 10096–10100 (1993).
Dohmen, R. J., Wu, P. & Varshavsky, A. Heat-inducible degron: a method for constructing temperature sensitive mutants. Science 263, 1273–1276 (1994).
Straight, A. F. et al. Mitosis in living budding yeast—anaphase A but no metaphase plate. Science 277, 574–578 (1997).
Waddle, J. A. et al. Movement of cortical actin patches in yeast. J. Cell Biol. 132, 861–870 (1996).
Weiss, E. & Winey, M. The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint. J. Cell Biol. 132, 111–123 (1996).
Acknowledgements
We thank C. Hardy, J. Haseloff, M. Johnston, A. Murray, A. Straight, D. Lew, M. A. Hoyt and M.Rose for strains and plasmids; and T. Karpova, K. Blumer, C. Hardy, R. Heil-Chapdelaine, A.Murray, S.Wente and M. Winey for advice and discussion. This work was supported by grants from the NIH. N.R.A. is a recipient of a Natural Sciences and Engineering Research Council of Canada postdoctoral fellowship. J.A.C. is an established investigator of the American Heart Association.
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Muhua, L., Adames, N., Murphy, M. et al. A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein. Nature 393, 487–491 (1998). https://doi.org/10.1038/31014
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DOI: https://doi.org/10.1038/31014
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