Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell . During telophase, the effects of prophase and prometaphase ( the nucleus and nuclear membrane disintegrate) are reversed. As the chromosomes reach the poles of the cell, a nuclear envelope reassembles around each set of chromatids , the nucleus reappears , and the chromosomes expand.begin to decompose back into chromatinwhich is present during the interface . The mitotic spindle is disassembled and the remaining spindle microtubules are depolymerized. Telophase accounts for about 2% of the duration of the cell cycle .


Cytokinesis usually begins before late telophase [1] and, when completed, separates the two daughter nuclei between a pair of distinct daughter cells.

Telophase is primarily induced by the dephosphorylation of mitotic cyclin dependent kinase (CDK) substrates.

Dephosphorylation of CDK substrates

Phosphorylation of protein targets of M- Cdks (mitotic cyclin-dependent kinases) drives spindle assembly, chromosome condensation and nuclear envelope breakdown in early mitosis. Dephosphorylation of these same substrates leads to spindle disassembly, chromosome decondensation and reformation of daughter nuclei in telophase. Establishing a degree of dephosphorylation permissive for telophase events requires both inactivation of Cdks and activation of phosphatases .


CDK inactivation primarily results in the destruction of its associated cyclins . The anaphase promoting complex (APC), also known as the cyclosome, [3] is targeted for proteolytic degradation of cyclins by a ubiquitin-ligase . Activated, CDC20-bound APC (APC/C CDC20 ) targets mitotic cyclins for degradation beginning in anaphase . [4]Experimental addition of non-degradable M-cyclin to cells induces cell cycle arrest at a post-anaphase/pre-telophase-like state, in which condensed chromosomes separate from the cell poles, an intact mitotic spindle, and nuclear envelope formation. There is no improvement. , This has been shown in frog ( Xenopus ) eggs, fruit flies ( Drosophila melanogaster ), budding ( Saccharomyces cerevisiae ) and fission ( Schizosaccharomyces pombe ) yeast, and in several human cell lines.

The requirement for phosphatase activation can be observed in budding yeast, which do not have redundant phosphatases for mitotic exit and are dependent on the phosphatase cdc14. Blocking cdc14 activation in these cells results in the same phenotypic arrest as blocking M-cyclin degradation.

Historically, it has been thought that anaphase and telophase are events that occur passively after satisfaction of the spindle-assembly checkpoint (SAC) that defines the metaphase–anaphase transition. [6]However, the existence of differential stages in cdc14 activity between anaphase and telophase is suggestive of additional, unexplored late-mitotic checkpoints. Cdc14 is activated by release into the nucleus by sequestration in the nucleolus, and subsequently by export to 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. Full release and maintained activation of CDC14 is achieved only after late anaphase in sufficient amounts (to trigger spindle disassembly and nuclear envelope assembly) by the distinct mitotic exit network (MEN) pathway.

Cdc14-mediated dephosphorylation activates downstream regulatory processes unique to telophase. For example, dephosphorylation of CDH1 allows APC/C to bind to CDH1. APC/C targets CDC20 for CDH1 proteolysis , resulting in a cellular switch from APC/C CDC20 to APC/C CDH1 activity. [5] APC/C continues to ubiquitinate mitotic cyclins along with CDH1- specific targets such as the yeast mitotic spindle component, Asc1, [2] and Cdc5 , whose degradation is required for cells to return to G1. phase . [7]

Additional mechanisms driving telophase

Alterations in the whole-cell phosphoprotein profile are only the most widespread of the many regulatory mechanisms contributing to the initiation of individual telophase events.

  • Anaphase-mediated distance of chromosomes from the metaphase plate can trigger spatial signals for the onset of telophase. [6]
  • An important regulator and effector of telophase is cdc48 (the homolog of yeast cdc48 is human p97, both structurally and functionally), a protein that employs its ATPase activity to mechanistically alter the target protein structure. Cdc48 is required for spindle disassembly, nuclear envelope assembly and chromosome decondensation. Cdc48 modified proteins structurally contain some ubiquitinated proteins that are thus targeted for these processes and are also involved in antibodies.

Mitotic spindle disassembly

The rupture of the mitotic spindle, common to the completion of mitosis in all eukaryotes, is the most commonly used event to define the anaphase-B to telophase transition, [2] [6] although it occurs before the onset of nuclear recombination. is to disassemble the axle. [11 1]

Spindle disassembly is an irreversible process that should not affect the final degradation, but rather the reorganization of the constituent microtubules; The microtubules detach from the kinetochores and spindle pole body and return to their interphase state.

00During telophase spindle depolymerization occurs from the plus end and thus, reversal of spindle assembly occurs. [12] The subsequent microtubule array assembly, in contrast to the polarized spindle, is interpolar. This is particularly evident in animal cells, which immediately, following mitotic spindle disassembly, must establish antiparallel bundles of microtubules, known as the central spindle, to regulate cytokinesis. [2] The ATPase p97 is required for the establishment of relatively stable and long interphase microtubule arrays after disassembly of the highly dynamic and relatively short mitotic ones. [9]

While spindle assembly has been well studied and characterized as a process where temporal structures are edited by SAC, the molecular basis of spindle disassembly is not understood in comparable detail. The late-mitotic dephosphorylation cascade of M-Cdk substrates by MEN is largely thought to be responsible for spindle disassembly. The phosphorylation states of microtubule stabilizing and destabilizing factors, as well as microtubule nucleators are key regulators of their activities. [9] For example, NuMA is a minus-end crosslinking protein and Cdk substrate whose dissociation from the microtubule is affected by its dephosphorylation during telophase.

A general model for spindle disassembly in yeast is that three functionally overlapping subprocesses of spindle disassembly, destabilization, and depolymerization are primarily affected by APC/C CDH1, microtubule-stabilizer-specific kinases, and plus-end directed microtubule depolymerase. There are. These effects are thought to be highly conserved between yeast and higher eukaryotes. APC/C CDH1Targets to crosslink microtubule-associated proteins (NuMA, Ase1, Cin1 and more). AuroraB (yeast IpI1) phosphorylates the spindle-associated stabilizing protein EB1 (yeast Bim1), which then dissociates from microtubules, and the destabilizer She1, which then associates with microtubules. Kinesin8 (yeast Kip3), an ATP-dependent depolymerase, accelerates microtubule depolarization at the plus end. It was shown that concurrent disruption of these mechanisms, but not of any one, results in dramatic spindle hyperstability during telophase, despite the diversity of mechanisms suggesting functional overlap.

nuclear envelope reconfiguration

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 destroyed during prophase and prometaphase and rebuilt during telophase, when the nuclear envelope reforms on the surface of separate sister chromatids. [14] [15] During prometaphase the nuclear membrane is fragmented and partially absorbed by the endoplasmic reticulum and the targeting of ER vesicles containing inner nuclear membrane proteins to chromatin is reversed during telophase. The membrane-forming vesicles aggregate directly onto the surface of chromatin, where they subsequently fuse into a continuous membrane. [2]

Ran-GTP is required for initial nuclear envelope assembly on the surface of chromosomes: it releases envelope components sequestered by importin β during early mitosis. Ran-GTP is localized near chromosomes during mitosis, but does not trigger the dissociation of nuclear envelope proteins from importin β until M-CDK targets are dephosphorylated at telophase. [2] These envelope components include several nuclear pore components, the most studied of which is the nuclear pore scaffold protein ELYS, which can recognize DNA regions enriched in A:T base pairs (in vitro), and therefore directly Can bind to DNA. [16] However, experiments in XenopusEgg extracts concluded that ELYS fails to associate with bare DNA and only directly binds histone dimers and nucleosomes. [17] After binding to chromatin, ELYS recruits the nuclear pore scaffold and other components of the nuclear pore trans-membrane proteins. The nuclear pore complex is assembled and integrated into the nuclear envelope in an organized manner, with the frequent addition of Nup107–160, POM121 and FG Nups.

It is debated whether the mechanism of nuclear membrane reconnection involves early nuclear pore assembly and subsequent recruitment of membrane vesicles around the pores or if the nuclear envelope is primarily formed from expanded ER cisternae, preceding nuclear pore. Assembly:

  • In cells where nuclear membrane fragments form in non-ER vesicles during mitosis, a Ran-GTP-dependent pathway may direct a population of these discrete vesicles to chromatin where they fuse to reform the nuclear envelope. [19] [16]
  • In cells where the nuclear membrane is absorbed into the endoplasmic reticulum during mitosis, expansion at the chromatin surface involves lateral expansion around chromatin with stabilization of the membrane. [20] Studies claiming this mechanism is a prerequisite for nuclear pore formation have found that bare-chromatin-associated Nup107–160 complexes exist in single units rather than assembled pre-pores. [21] [16]

The envelope smooths and expands after the entire chromatid set has been engulfed. This is probably due to the import of laminin from the nuclear pores, which can be placed within a continuous membrane. The nuclear envelope of Xenopus egg extracts did not smooth out when nuclear import of the lamin was inhibited, remaining closely linked to wrinkled and condensed chromosomes. [22] However, in the case of ER lateral expansion, nuclear import is initiated before nuclear envelope reconnection is complete, forming a temporary inter-nuclear protein gradient between the distal and medial aspects of the nucleus. . [18]

The dissociated lamin subunits in prophase are inactivated and sequestered during mitosis. Laminar reassembly (by methylation as well as lamin dephosphorylation triggered by esterification of the COOH residue on lamin-B). Lamin-B can target chromatin as early as mid-anaphase. During telophase, when nuclear import is re-established, lamin-A reformer enters the nucleus, but continues to slowly assemble in the peripheral lamina for several hours throughout G1 phase. [16]

Xenopus egg extracts and human cancer cell lines have been the primary models used to study nuclear envelope reconnection. [18]

Yeast lacks vitamins; Their nuclear envelope remains intact during mitosis and nuclear division occurs during cytokinesis. [23] [11]

chromosome aberrations

Chromosome decondensation (also known as relaxation or decondensation) into extended chromatin is essential for the cell’s restoration of interphase processes, and occurs in parallel with nuclear envelope assembly during telophase in many eukaryotes. [2] Male-mediated CDK dephosphorylation is required for chromosome decondensation. [2] [5]

In vertebrates, chromosomal aberrations begin only after nuclear import has been reestablished. If fragment transport through nuclear pores is inhibited, chromosomes remain condensed after cytokinesis, and cells fail to re-enter the next S phase. [16] In mammals, DNA licensing to S phase (association of chromatin to several protein factors required for its replication) also occurs coincidentally with maturation of the nuclear envelope during late telophase. [24] [25] can be attributed to this and provides evidence for the restoration of interphase nuclear and cytoplasmic protein localization of the nuclear import machinery during telophase.