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Telophase () is the final stage in both
meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
and
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
in a
eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
. During telophase, the effects of
prophase Prophase () is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin retic ...
and
prometaphase Prometaphase is the phase of mitosis following prophase and preceding metaphase, in eukaryotic somatic cells. In prometaphase, the nuclear membrane breaks apart into numerous "membrane vesicles", and the chromosomes inside form protein struc ...
(the
nucleolus The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of sig ...
and nuclear membrane disintegrating) are reversed. As
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
s reach the cell poles, a
nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membrane ...
is re-assembled around each set of
chromatid A chromatid (Greek ''khrōmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chro ...
s, the
nucleoli The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of sig ...
reappear, and chromosomes begin to decondense back into the expanded
chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
that is present during
interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...
. The
mitotic spindle In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...
is disassembled and remaining spindle
microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
s are depolymerized. Telophase accounts for approximately 2% of the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
's duration.
Cytokinesis Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...
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 In biochemistry, dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deac ...
of mitotic
cyclin-dependent kinase Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They a ...
(Cdk) substrates.


Dephosphorylation of Cdk substrates

The
phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
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
phosphatase In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester, monoester into a phosphate ion and an Alcohol (chemistry), alcohol. Because a phosphatase enzyme catalysis, catalyzes the hydrolysis of its Substrate ...
s. Cdk inactivation is primarily the result of the destruction of its associated
cyclin Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. Etymology Cyclins were originally disco ...
. Cyclins are targeted for
proteolytic degradation Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
by the
anaphase promoting complex Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin ...
(APC), also known as the cyclosome, a ubiquitin-ligase. The active,
CDC20 The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the ''CDC20'' gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (APC/ ...
-bound APC (APC/CCDC20) targets mitotic cyclins for degradation starting in
anaphase Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall maxim ...
. 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 ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...
)'' eggs, fruit flies ('' Drosophilla melanogaster''), budding (''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'') and fission (''
Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
'') 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 ''Cdc14'' and Cdc14 are a gene and its protein product respectively. Cdc14 is found in most of the eukaryotes. Cdc14 was defined by Hartwell in his famous screen for loci that control the cell cycle of Saccharomyces cerevisiae. Cdc14 was later show ...
. Blocking cdc14 activation in these cells results in the same phenotypic arrest as does blocking M-cyclin degradation. Historically, it has been thought that
anaphase Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall maxim ...
and telophase are events that occur passively after satisfaction of the spindle-assembly checkpoint (SAC) that defines the
metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, align ...
-anaphase transition. 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/CCDH1 targets CDC20 for proteolysis, resulting in a cellular switch from APC/CCDC20 to APC/CCDH1 activity. The ubiquitination of mitotic cyclins continues along with that of APC/CCDH1-specific targets such as the yeast mitotic spindle component, Ase1, and cdc5, the degradation of which is required for the return of cells to the
G1 phase The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leadi ...
.


Additional mechanisms driving telophase

A shift in the whole-cell
phosphoprotein A phosphoprotein is a protein that is posttranslationally modified by the attachment of either a single phosphate group, or a complex molecule such as 5'-phospho-DNA, through a phosphate group. The target amino acid is most often serine, threonin ...
profile is only the broadest of many regulatory mechanisms contributing to the onset of individual telophase events. * The anaphase-mediated distancing of chromosomes from the metaphase plate may trigger spatial cues for the onset of telophase. * An important regulator and effector of telophase is cdc48 (homologous to yeast cdc48 is human p97, both structurally and functionally), a protein that mechanically employs its
ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
activity to alter target protein conformation. Cdc48 is necessary for spindle disassembly, nuclear envelope assembly, and chromosome decondensation. Cdc48 modifies proteins structurally involved in these processes and also some ubiquitinated proteins which are thus targeted to the
proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by w ...
.


Mitotic spindle disassembly

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, although the initiation of nuclear reassembly tends to precede that of spindle disassembly. Spindle disassembly is an irreversible process which must effect not the ultimate degradation, but the reorganization of constituent microtubules; microtubules are detached from
kinetochore A kinetochore (, ) is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and ...
s 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 The central spindle is a microtubule based structure, which forms in between segregating chromosomes during anaphase where the two sets of microtubules, emanating from opposite halves of the cell, overlap, and become arranged into antiparallel bundl ...
'' in order to regulate cytokinesis. The ATPase p97 is required for the establishment of the relatively stable and long interphase microtubule arrays following disassembly of the highly dynamic and relatively short mitotic ones. While spindle assembly has been well studied and characterized as a process where tentative structures are edified by the SAC, the molecular basis of spindle disassembly is not understood in comparable detail. The late-mitotic dephosphorylation cascade of M-Cdk substrates by the MEN is broadly held 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. For example, NuMA is a minus-end crosslinking protein and Cdk substrate whose dissociation from the microtubule is effected by its dephosphorylation during telophase. A general model for spindle disassembly in yeast is that the three functionally overlapping subprocesses of spindle disengagement, destabilization, and depolymerization are primarily effected by APC/CCDH1, microtubule-stabilizer-specific kinases, and plus-end directed microtubule depolymerases, respectively. These effectors are known to be highly conserved between yeast and higher eukaryotes. The APC/CCDH1 targets crosslinking 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, accelerate microtubule depolymerization at the plus end. It was shown the concurrent disruption of these mechanisms, but not of any one, results in dramatic spindle hyperstability during telophase, suggesting functional overlap despite the diversity of the mechanisms.


Nuclear envelope reassembly

The main components of the nuclear envelope are a double membrane,
nuclear pore complexes A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes ...
, and a
nuclear lamina The nuclear lamina is a dense (~30 to 100  nm thick) fibrillar network inside the nucleus of eukaryote cells. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the 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 The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
during prometaphase and the targeting of inner nuclear membrane protein-containing ER
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
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 Fuse or FUSE may refer to: Devices * Fuse (electrical), a device used in electrical systems to protect against excessive current ** Fuse (automotive), a class of fuses for vehicles * Fuse (hydraulic), a device used in hydraulic systems to protect ...
laterally into a continuous membrane. Ran-GTP is required for early nuclear envelope assembly at the surface of the chromosomes: it releases envelope components sequestered by importin β during early mitosis. Ran-GTP localizes near chromosomes throughout mitosis, but does not trigger the dissociation of nuclear envelope proteins from importin β until M-Cdk targets are dephosphorylated in telophase. 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 rich in A:T base pairs (in vitro), and may therefore bind directly to the DNA. However, experiments in ''Xenopus'' egg extracts have concluded that ELYS fails to associate with bare DNA and will only directly bind
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
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. * In cells where the nuclear membrane is absorbed into the endoplasmic reticulum during mitosis, reassembly involves the lateral expansion around the chromatin with stabilization of the expanding membrane over the surface of the chromatin. 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. The envelope smoothens and expands following its enclosure of the whole chromatid set. This probably occurs due to the nuclear pores’ import of
lamin Lamins, also known as nuclear lamins are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the ...
, which can be retained within a continuous membrane. The nuclear envelopes of ''Xenopus'' egg extracts failed to smoothen when nuclear import of lamin was inhibited, remaining wrinkled and closely bound to condensed chromosomes. 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. Lamin subunits disassembled in prophase are inactivated and sequestered during mitosis. Lamina reassembly is triggered by lamin dephosphorylation (and additionally by methyl-
esterification In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
of COOH residues on lamin-B). Lamin-B can target chromatin as early as mid-anaphase. During telophase, when nuclear import is reestablished, lamin-A enters the reforming nucleus but continues to slowly assemble into the peripheral lamina over several hours in throughout the G1 phase. ''Xenopus'' egg extracts and human cancer cell lines have been the primary models used for studying nuclear envelope reassembly. Yeast lack lamins; their nuclear envelope remains intact throughout mitosis and nuclear division happens during cytokinesis.


Chromosome decondensation

Chromosome decondensation (also known as relaxation or decompaction) into expanded chromatin is necessary for the cell's resumption of interphase processes, and occurs in parallel to nuclear envelope assembly during telophase in many eukaryotes. MEN-mediated Cdk dephosphorylation is necessary for chromosome decondensation. In vertebrates, chromosome decondensation is initiated only after
nuclear import A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines ...
is reestablished. If lamin transport through nuclear pores is prevented, chromosomes remain condensed following cytokinesis, and cells fail to reenter the next S phase. In mammals, DNA licensing for S phase (the association of chromatin to the multiple protein factors necessary for its replication) also occurs coincidentally with the maturation of the nuclear envelope during late telophase. 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


External links

* {{Cell cycle Cell cycle Mitosis de:Mitose#Telophase