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Mad2 and Bub2 are both activated by the kinase Mps1 but induce arrest at different stages of mitosis. The Mad2 (spindle assembly) pathway inhibits the metaphase to anaphase transition by preventing APC^Cdc20-dependent Pds1 ubiquitination while the Bub2 pathway inhibits mitotic exit by preventing APC^Cdh1-dependent B-type cyclin degradation and by maintaining Cdk activity. Both branches are required for indefinite arrest, although a significant delay in mitosis can be invoked when either pathway is activated. Photomicrographs of onion root meristematic cells depict the mitotic stages. See text for detailed descriptions.

The kinetochores of prometaphase chromosomes (a-c and the left cell in g) become phosphorylated forming a 3F3/2 antibody-reactive epitope (open circles). The phospho-epitope is lost (filled circles) as chromosomes attach to the mitotic spindle forming the metaphase plate (b-d). This inactivates the spindle assembly checkpoint and cells begin anaphase roughly 20 minutes later (e-f and the right cell in g). Micrographs show onion root meristematic cells. The left cell is represented schematically in c, in which one chromosome has not congressed (also see arrow in g).

A summary of the five checkpoints that are discussed in detail (see magnifying glass). In mammals the G2/M transition is regulated by at least 2 non-DNA damage checkpoint pathways (1 and 2). These prevent the initiation of mitosis until DNA replication is complete (1, S-phase checkpoint), and until DNA is sufficiently decatenated (2, Topoisomerase II-dependent checkpoint). The Chfr checkpoint (3) appears to restrict chromosome condensation when spindle assembly is perturbed. Also within mitosis the spindle assembly checkpoint (4) delays the onset of anaphase until all the chromosomes of the karyotype have been correctly arranged on the mitotic spindle. In budding yeast, similar checkpoint controls inhibit the onset of anaphase rather than preventing passage beyond the G2/M transition. Therefore the G2/M transition in mammals and the metaphase-anaphase transition in budding yeast are somewhat analogous. Indeed, sensor and signaling components of these checkpoint pathways are conserved. However, the checkpoint targets differ between mammals and budding yeast, and the topoisomerase II-dependent checkpoint is not functional in budding yeast. Exit from mitosis (5) is also under checkpoint control, to ensure that anaphase has been completed before cell division. Photomicrographs of onion root meristematic cells depict the mitotic stages. The cartoons compare cell cycle stages in budding yeast and mammals.