Mitosis Mitosis is the process, in the cell cycle,
by which a cell duplicates into two genetically identical daughter cells.
In mitosis, chromosomes in the cell nucleus are separated into two identical sets of chromosomes,
each in its own nucleus.
In general, mitosis is followed immediately by cytokinesis, which divides the cytoplasm,
organelles, and cell membrane, and later karyokinesis, which divides the nucleus, dividing the cell
into two new cells containing roughly equal shares of these cellular components.
Mitosis and cytokinesis together define the mitotic phase of the cell cycle—the division
of the mother cell into two daughter cells, genetically identical to each other and to
their parent cell.
This accounts for approximately 20% of the cell cycle.
Mitosis occurs only in eukaryotic cells and the process varies in different groups.
For example, animals undergo an "open" mitosis, where the nuclear envelope breaks down before
the chromosomes separate, while fungi such as Aspergillus nidulans and Saccharomyces
cerevisiae (yeast) undergo a "closed" mitosis, where chromosomes divide within an intact
cell nucleus.
Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.
The process of mitosis is fast and highly complex.
The sequence of events is divided into stages corresponding to the completion of one set
of activities and the start of the next.
These stages are prophase, prometaphase, metaphase, anaphase, and telophase.
During mitosis, the pairs of chromatids condense and attach to fibers that pull the sister
chromatids to opposite sides of the cell.
The cell then divides in cytokinesis, to produce two daughter cells.
Because cytokinesis often occurs in conjunction with mitosis, "mitosis" is often used interchangeably
with "mitotic phase".
However, there are many cells where mitosis and cytokinesis occur separately, forming
single cells with multiple nuclei.
The most notable occurrence of this is among the fungi and slime molds, but is found in
various groups.
Even in animals, cytokinesis and mitosis may occur independently, for instance during certain
stages of fruit fly embryonic development.
Errors in mitosis can either kill a cell through apoptosis or cause mutations.
Certain types of cancer can arise from such mutations.
Mitosis was discovered in frog, rabbit, and cat cornea cells in 1873 and described for
the first time by the Polish histologist Wacław Mayzel in 1875.
The term is derived from the Greek word μίτος mitos "warp thread".
Overview of cell cycle in relation to mitosis The primary result of mitosis is the transferring
of the parent cell's genome into two daughter cells.
These two cells are identical and do not differ in any way.
The genome is composed of a number of chromosomes—complexes of tightly coiled DNA that contain genetic
information vital for proper cell function.
Because each resultant daughter cell should be genetically identical to the parent cell,
the parent cell must make a copy of each chromatid before mitosis.
This occurs during the S phase of interphase, the period that precedes the mitotic phase
in the cell cycle where preparation for mitosis occurs.
The two identical chromatids resulting from chromatid duplication are called sister chromatids.
They are held together by a specialized region of the chromosome: a DNA sequence called the
centromere.
Mitosis begins when the chromosomes condense and become visible.
In most eukaryotes, the nuclear membrane, which segregates the DNA from the cytoplasm,
disintegrates into membrane vesicles.
The nucleolus, which makes ribosomes in the cell, also dissolves.
The chromosomes align themselves in a line spanning the cell.
Microtubules—in essence, miniature strings—splay out from opposite ends of the cell and shorten,
pulling apart the sister chromatids of each chromosome.
Sister chromatids at this point are called daughter chromosomes.
As the cell elongates, corresponding daughter chromosomes are pulled toward opposite ends.
A new nuclear membrane forms around the separated daughter chromosomes.
As mitosis completes, the cell begins cytokinesis.
In animal cells, the cell pinches inward where the imaginary line used to be (the area of
the cell membrane that pinches to form the two daughter cells is called the cleavage
furrow), separating the two developing nuclei.
In plant cells, the daughter cells will construct a dividing cell wall.
Eventually, the parent cell will be split in half, giving rise to two daughter cells,
each with a replica of the original genome.
Prokaryotic cells undergo a process called binary fission, which is very much different
from the process of mitosis, because there are no nuclear dynamics and chromosomes aren't
linear.
Phases of cell cycle and mitosis Interphase
The mitotic phase is a relatively short period of the cell cycle.
It alternates with the much longer interphase, where the cell prepares itself for the process
of cell division.
Interphase is divided into three phases: G1 (first gap), S (synthesis), and G2 (second
gap).
During all three phases, the cell grows by producing proteins and cytoplasmic organelles.
However, chromosomes are replicated only during the S phase.
Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows
more and prepares for mitosis (G2), and finally it divides (M) before restarting the cycle.
All these phases in the cell cycle are highly regulated, mainly via proteins.
The phases follow one another in strict order and there are "checkpoints" that give the
cell the cues to proceed from one phase to another.
There is also a fourth section in Interphase where the cell has the option to enter G0.
Cells continue on through this cell cycle until they become too crowded; at that point
they will exit the cell cycle and enter G0.
This reaction is called contact inhibition or density-dependent inhibition.
Altogether interphase takes up roughly 90% of a cell's lifespan.
Preprophase (Plant Cells) In plant cells only, prophase is preceded
by a pre-prophase stage.
In highly vacuolated plant cells, the nucleus has to migrate into the center of the cell
before mitosis can begin.
This is achieved through the formation of a phragmosome, a transverse sheet of cytoplasm
that bisects the cell along the future plane of cell division.
In addition to phragmosome formation, preprophase is characterized by the formation of a ring
of microtubules and actin filaments (called preprophase band) underneath the plasma membrane
around the equatorial plane of the future mitotic spindle.
This band marks the position where the cell will eventually divide.
The cells of higher plants (such as the flowering plants) lack centrioles; instead, microtubules
form a spindle on the surface of the nucleus and are then organized into a spindle by the
chromosomes themselves, after the nuclear membrane dissolves.
The preprophase band disappears during nuclear membrane dissolution and spindle formation
in prometaphase.
Prophase During this stage the cell prepares to divide
by dissolving the membrane around the nucleus and the chromatin condenses into chromosomes.
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin.
At the onset of prophase, chromatin fibers become tightly coiled, condensing into discrete
chromosomes.
It is crucial for the reader to note that chromatin is a complex consisting of both
DNA and specific proteins.
Since the genetic material has already been duplicated earlier in S phase, the replicated
chromosomes have two sister chromatids, bound together at the centromere by the cohesin
protein complex.
Chromosomes are typically visible at high magnification through a light microscope.
Also inside the nucleus, the nucleolus in the nucleus disappears from view.
This is noteworthy because the cell does not need to divide the nucleolus right away.
It will later reform when the nucleus divides completely.
Close to the nucleus are structures called centrosomes, consisting of a pair of centrioles,
and actin, a halo of microtubule fragments.
Centrioles are found in most eukaryotic animal cells.
The centrosome is the coordinating center for the cell's microtubules.
A cell inherits a single centrosome at cell division, which is replicated by the cell
with the help of the nucleus before a new mitosis begins, giving a pair of centrosomes.
The two centrosomes nucleate microtubules (which may be thought of as cellular ropes
or poles) to form the spindle by polymerizing soluble tubulin.
Molecular motor proteins then push the centrosomes along these microtubules to opposite sides
of the cell.
Although centrioles help organize microtubule assembly, they are not essential for the formation
of the spindle, since they are absent from plants, and centrosomes are not always used
in mitosis.
Prometaphase Note: Prometaphase is sometimes included as
part of the end of prophase or part of early metaphase.
During early prometaphase, the nuclear membrane disintegrates and microtubules invade the
nuclear space.
This is called open mitosis, and it occurs in most multicellular organisms.
Fungi and some protists, such as algae or trichomonads, undergo a variation called closed
mitosis where the spindle forms inside the nucleus, or its microtubules are able to penetrate
an intact nuclear membrane, which stays intact.
In late prometaphase, each chromosome forms two kinetochores at its centromere, one attached
at each chromatid.
A kinetochore is a complex protein structure that is analogous to a ring for the microtubule
hook; it is the point where microtubules attach themselves to the chromosome.
Although the kinetochore structure and function are not fully understood, it is known that
it contains some form of molecular motor.
When a microtubule connects with the kinetochore, the motor activates, using energy from ATP
to "crawl" up the tube toward the originating centrosome.
This motor activity, coupled with polymerisation and depolymerisation of microtubules, provides
the pulling force necessary to later separate the chromosome's two chromatids.
When the spindle grows to sufficient length, kinetochore microtubules begin searching for
kinetochores to attach to.
A number of nonkinetochore microtubules find and interact with corresponding nonkinetochore
microtubules from the opposite centrosome to form the mitotic spindle.
In the fishing pole analogy, the kinetochore would be the "hook" that catches a sister
chromatid or "fish".
The centrosome acts as the "reel" that draws in the spindle fibers or "fishing line".
It is also one of the main phases of mitosis because without it cytokinesis would not be
able to occur.
Metaphase Metaphase came from the Greek word μετα
meaning "after."
After the microtubules have found and attached to the kinetochores in prometaphase, the two
centrosomes start pulling the chromosomes through their attached centromeres towards
the two ends of the cell.
As a result, the chromosomes come under longitudinal tension from the two ends of the cell.
The centromeres of the chromosomes, in some sense, convene along the metaphase plate or
equatorial plane, an imaginary line that is right in between the two centrosome poles.
This line is called the spindle equator.
This even alignment is due to the counterbalance of the pulling powers generated by the opposing
kinetochores, analogous to a tug-of-war between people of equal strength.
In certain types of cells, chromosomes do not line up at the metaphase plate and instead
move back and forth between the poles randomly, only roughly lining up along the midline.
Because proper chromosome separation requires that every kinetochore be attached to a bundle
of microtubules (spindle fibres), it is thought that unattached kinetochores generate a signal
to prevent premature progression to anaphase without all chromosomes being aligned.
The signal creates the mitotic spindle checkpoint.
Anaphase When every kinetochore is attached to a cluster
of microtubules and the chromosomes have lined up along the metaphase plate, the cell proceeds
to anaphase (from the Greek word ανα meaning "up," "against," "back," or "re-").
Two events then occur: First, the proteins that bind sister chromatids together are cleaved.
These sister chromatids now become separate daughter chromosomes, and are pulled apart
by shortening kinetochore microtubules and move toward the respective centrosomes to
which they are attached.
The cleaved centromeres go first while the chromatids trail behind.
They all look as if they are trying to grab at their partners, because they become shaped
like a V. Next, the polar microtubules elongate, pulling
the centrosomes (and the set of chromosomes to which they are attached) apart to opposite
ends of the cell.
The force that causes the centrosomes to move toward the ends of the cell is still unknown,
although there is a theory that suggests that the rapid assembly and breakdown of microtubules
may cause this movement.
At the end of anaphase the kinetochore microtubules all degrade.
Telophase Telophase (from the Greek word τελος
meaning "end") is a reversal of prophase and prometaphase events.
It "cleans up" the after effects of mitosis.
At telophase, the polar microtubules continue to lengthen, elongating the cell even more.
Corresponding daughter chromosomes attach at opposite ends of the cell.
A new nuclear membrane, using the membrane vesicles of the parent cell's old nuclear
membrane, forms around each set of separated daughter chromosomes (though the membrane
does not enclose the centrosomes) and the nucleolus reappears.
Both sets of chromosomes, now surrounded by new nuclei, begin to "relax" or decondense
back into chromatin.
Mitosis is complete, but cell division is not.
Cytokinesis Cytokinesis is often mistakenly thought to
be the final part of telophase; however, cytokinesis is a separate process that begins at the same
time as telophase.
Cytokinesis is not, in the technical sense, even a phase of mitosis but rather a separate
process, necessary for completing cell division.
In animal cells, a cleavage furrow (pinch) containing a contractile ring develops where
the metaphase plate used to be, pinching off the separated nuclei.
In both animal and plant cells, cell division is also driven by vesicles derived from the
Golgi apparatus, which move along microtubules to the middle of the cell.
In plants, this structure coalesces into a cell plate at the center of the phragmoplast
and develops into a cell wall, separating the two nuclei.
The phragmoplast is a microtubule structure typical for higher plants, whereas some green
algae use a phycoplast microtubule array during cytokinesis.
Each daughter cell has a complete copy of the genome of its parent cell.
The end of cytokinesis marks the end of the M-phase.
Significance Mitosis is important for the maintenance of
the chromosomal set; each cell formed receives chromosomes that are alike in composition
and equal in number to the chromosomes of the parent cell.
Mitosis occurs in the following circumstances: Consequences of errors
Although errors in mitosis are rare, the process may go wrong, especially during early cellular
divisions in the zygote.
Mitotic errors can be especially dangerous to the organism because future offspring from
this parent cell will carry the same disorder.
In nondisjunction, a chromosome may fail to separate during anaphase.
One daughter cell will receive both sister chromosomes and the other will receive none.
This results in the former cell having three chromosomes containing the same genes (two
sisters and a homologue), a condition known as trisomy, and the latter cell having only
one chromosome (the homologous chromosome), a condition known as monosomy.
These cells are considered aneuploid, a condition often associated with cancer.
On occasion when cells experience nondisjunction, they fail to complete cell division and retain
both nuclei in one cell, resulting in binucleated cells.
Mitosis is a demanding process for the cell, which goes through dramatic changes in ultrastructure,
its organelles disintegrate and reform in a matter of hours, and chromosomes are jostled
constantly by probing microtubules.
Occasionally, chromosomes may become damaged.
An arm of the chromosome may be broken and the fragment lost, causing deletion.
The fragment may incorrectly reattach to another, non-homologous chromosome, causing translocation.
It may reattach to the original chromosome, but in reverse orientation, causing inversion.
Or, it may be treated erroneously as a separate chromosome, causing chromosomal duplication.
The effect of these genetic abnormalities depends on the specific nature of the error.
Endomitosis Endomitosis is a variant of mitosis without
nuclear or cellular division, resulting in cells with many copies of the same chromosome
occupying a single nucleus.
This process may also be referred to as endoreduplication and the cells as endoploid.
An example of a cell that goes through endomitosis is the megakaryocyte.
Timeline in pictures Real mitotic cells can be visualized through
the microscope by staining them with fluorescent antibodies and dyes.
These light micrographs are included below.