Several components of the checkpoint have been identified through budding yeast genetics. Defects in spindle assembly or chromosome attachment prevent the onset of anaphase by activating the spindle checkpoint. 1997).įormation of an intact mitotic spindle and attachment of all sister chromatids to the spindle before anaphase occurs is crucial to proper chromosome segregation. Proteolysis of the anaphase inhibitor Pds1p induces chromatids to separate and move to opposite spindle poles ( Cohen-Fix et al., 1996), and the destruction of Clb2p and Ase1p are required for cells to exit from mitosis ( Surana et al., 1993 Juang et al. Activation of Cdc28 protein kinase leads to mitotic spindle formation. Mitosis in most eukaryotes is regulated by a cyclin-dependent kinase, which is activated by association with the mitotic cyclins, and is encoded by CDC28 in the budding yeast Saccharomyces cerevisiae and the Cdc2 gene of other organisms.
Defects in checkpoints compromise the faithful transmission of genetic information and have been shown to play an important role in tumor progression ( Hartwell and Kastan, 1994 Cahill et al., 1998).
These regulatory linkages are due to cell cycle checkpoints ( Hartwell and Weinert, 1989 Elledge, 1996 Rudner and Murray, 1996), mechanisms that arrest the cell cycle if the preceding events have not been completed or if damage has occurred.
For example, mitosis occurs only after DNA synthesis has completed, and chromosome segregation does not begin until all the chromosomes have been correctly aligned on the mitotic spindle. Cell cycle progression is a highly ordered and tightly regulated process.
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