Although sister-chromatid separation initiates the chromosome movements of anaphase A, other mechanisms also ensure correct chromosome movements in anaphase A and spindle elongation in anaphase B. Most importantly, the completion of a normal anaphase depends on the dephosphorylation of Cdk substrates, which in most cells results from the APC/C-dependent destruction of cyclins. If M-cyclin destruction is prevented—by the production of a mutant form that is not recognized by the APC/C, for example—sister-chromatid separation generally occurs, but the chromosome movements and microtubule behavior of anaphase are abnormal.
The relative contributions of anaphase A and anaphase B to chromosome segregation vary greatly, depending on the cell type. In mammalian cells, anaphase B begins shortly after anaphase A and stops when the spindle is about twice its metaphase length; in contrast, the spindles of yeasts and certain protozoa primarily use anaphase B to separate the chromosomes at anaphase, and their spindles elongate to up to 15 times their metaphase length.
Figure 17–39 Mad2 protein on unattached kinetochores. This fluorescence micrograph shows a mammalian cell in prometaphase, with the mitotic spindle in green and the sister chromatids in blue. One sister-chromatid pair is attached to only one pole of the spindle. staining with anti-mad2 antibodies indicates that mad2 is bound to the kinetochore of the unattached sister chromatid (red dot, indicated by red arrow). a small amount of mad2 is associated with the kinetochore of the sister chromatid that is attached to the spindle pole (pale dot, indicated by white arrow). (From J.C. Waters et al., J. Cell Biol. 141:1181–1191, 1998. With permission from the authors.) segregated Chromosomes are packaged in daughter nuclei at Telophase
By the end of anaphase, the daughter chromosomes have segregated into two equal groups at opposite ends of the cell. In telophase, the final stage of mitosis, the two sets of chromosomes are packaged into a pair of daughter nuclei. The first major event of telophase is the disassembly of the mitotic spindle, followed by the re-formation of the nuclear envelope. Initially, nuclear membrane fragments associate with the surface of individual chromosomes. These membrane fragments fuse to partly enclose clusters of chromosomes and then coalesce to reform the complete nuclear envelope. Nuclear pore complexes are incorporated into the envelope, the nuclear lamina re-forms, and the envelope once again becomes continuous with the endoplasmic reticulum. Once the nuclear envelope has re-formed, the pore complexes pump in nuclear proteins, the nucleus expands, and the mitotic chromosomes are reorganized into their interphase state, allowing gene transcription to resume. A new nucleus has been created, and mitosis is complete. All that remains is for the cell to complete its division into two.
We saw earlier that phosphorylation of various proteins by M-Cdk promotes spindle assembly, chromosome condensation, and nuclear-envelope breakdown in early mitosis. It is thus not surprising that the dephosphorylation of these same proteins is required for spindle disassembly and the re-formation of daughter nuclei in telophase. In principle, these dephosphorylations and the completion of mitosis could be triggered by the inactivation of Cdks, the activation of phosphatases, or both. Although Cdk inactivation—resulting primarily from cyclin destruction—is mainly responsible in most cells, some cells also rely on activation of phosphatases. In budding yeast, for example, the completion of mitosis depends on the activation of a phosphatase called Cdc14, which dephosphorylates a subset of Cdk substrates involved in anaphase and telophase.