alt=A detailed diagram of telophase|thumb|upright=1.35|Diagram of telophase

Telophase () is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase (the nucleolus and nuclear membrane disintegrating) are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.

Cytokinesis typically begins before late telophase and, when complete, segregates the two daughter nuclei between a pair of separate daughter cells.

Telophase is primarily driven by the dephosphorylation of mitotic cyclin-dependent kinase (Cdk) substrates.

Dephosphorylation of Cdk substrates

The phosphorylation of the protein targets of M-Cdks (Mitotic Cyclin-dependent Kinases) drives spindle assembly, chromosome condensation and nuclear envelope breakdown in early mitosis. The dephosphorylation of these same substrates drives spindle disassembly, chromosome decondensation and the reformation of daughter nuclei in telophase. Establishing a degree of dephosphorylation permissive to telophase events requires both the inactivation of Cdks and the activation of phosphatases.

Cdk inactivation is primarily the result of the destruction of its associated cyclin. Cyclins are targeted for proteolytic degradation by the anaphase promoting complex (APC), also known as the cyclosome, a ubiquitin-ligase. The active, CDC20-bound APC (APC/C<sup>CDC20</sup>) targets mitotic cyclins for degradation starting in anaphase. Experimental addition of non-degradable M-cyclin to cells induces cell cycle arrest in a post-anaphase/pre-telophase-like state with condensed chromosomes segregated to cell poles, an intact mitotic spindle, and no reformation of the nuclear envelope. This has been shown in frog (Xenopus) eggs, fruit flies (Drosophilla melanogaster), budding (Saccharomyces cerevisiae) and fission (Schizosaccharomyces pombe) yeast, and in multiple human cell lines.

The requirement for phosphatase activation can be seen in budding yeast, which do not have redundant phosphatases for mitotic exit and rely on the phosphatase cdc14. Blocking cdc14 activation in these cells results in the same phenotypic arrest as does blocking M-cyclin degradation. However, the existence of differential phases to cdc14 activity between anaphase and telophase is suggestive of additional, unexplored late-mitotic checkpoints. Cdc14 is activated by its release into the nucleus, from sequestration in the nucleolus, and subsequent export into the cytoplasm. The Cdc-14 Early Anaphase Release pathway, which stabilizes the spindle, also releases cdc14 from the nucleolus but restricts it to the nucleus. Complete release and maintained activation of cdc14 is achieved by the separate Mitotic Exit Network (MEN) pathway to a sufficient degree (to trigger the spindle disassembly and nuclear envelope assembly) only after late anaphase.

Cdc14-mediated dephosphorylation activates downstream regulatory processes unique to telophase. For example, the dephosphorylation of CDH1 allows the APC/C to bind CDH1. APC/C<sup>CDH1</sup> targets CDC20 for proteolysis, resulting in a cellular switch from APC/C<sup>CDC20</sup> to APC/C<sup>CDH1</sup> activity.

Mitotic spindle disassembly

thumb|Stages of late M phase in a vertebrate cell

The breaking of the mitotic spindle, common to the completion of mitosis in all eukaryotes, is the event most often used to define the anaphase-B to telophase transition,

Spindle disassembly is an irreversible process which must effect not the ultimate degradation, but the reorganization of constituent microtubules; microtubules are detached from kinetochores and spindle pole bodies and return to their interphase states.

Spindle depolymerization during telophase occurs from the plus end and is, in this way, a reversal of spindle assembly. Subsequent microtubule array assembly is, unlike that of the polarized spindle, interpolar. This is especially apparent in animal cells which must immediately, following mitotic spindle disassembly, establish the antiparallel bundle of microtubules known as the central spindle in order to regulate cytokinesis.

Nuclear envelope reassembly

The main components of the nuclear envelope are a double membrane, nuclear pore complexes, and a nuclear lamina internal to the inner nuclear membrane. These components are dismantled during prophase and prometaphase and reconstructed during telophase, when the nuclear envelope reforms on the surface of separated sister chromatids. The nuclear membrane is fragmented and partly absorbed by the endoplasmic reticulum during prometaphase and the targeting of inner nuclear membrane protein-containing ER vesicles to the chromatin occurs during telophase in a reversal of this process. Membrane-forming vesicles aggregate directly to the surface of chromatin, where they fuse laterally into a continuous membrane. However, experiments in Xenopus egg extracts have concluded that ELYS fails to associate with bare DNA and will only directly bind histone dimers and nucleosomes. After binding to chromatin, ELYS recruits other components of the nuclear pore scaffold and nuclear pore trans-membrane proteins. The nuclear pore complex is assembled and integrated in the nuclear envelope in an organized manner, consecutively adding Nup107-160, POM121, and FG Nups.

It is debated whether the mechanism of nuclear membrane reassembly involves initial nuclear pore assembly and subsequent recruitment of membrane vesicles around the pores or if the nuclear envelope forms primarily from extended ER cisternae, preceding nuclear pore assembly:

  • In cells where the nuclear membrane fragments into non-ER vesicles during mitosis, a Ran-GTP–dependent pathway can direct these discrete vesicle populations to chromatin where they fuse to reform the nuclear envelope. Studies claiming this mechanism is a prerequisite to nuclear pore formation have found that bare-chromatin-associated Nup107–160 complexes are present in single units instead of as assembled pre-pores. However, in the case of ER lateral expansion, nuclear import is initiated before completion of the nuclear envelope reassembly, leading to a temporary intra-nuclear protein gradient between the distal and medial aspects of the forming nucleus. This can be attributed to and provides evidence for the nuclear import machinery's reestablishment of interphase nuclear and cytoplasmic protein localizations during telophase.

See also

References

de:Mitose#Telophase