Mitosis

The name “mitosis” comes from the Greek word mitos, meaning “thread.” The name was coined in 1882 by
the German biologist Walther Flemming to describe the threadlike chromosomes that mysteriously appeared
in animal cells just before they divided in two.
Mitosis (known as karyokinesis) is a process of nuclear division in which the replicated DNA molecules
of each chromosome are faithfully segregated into two nuclei. Chromosomes replicated during the Synthetic
phase are divided in such a way as to ensure that each daughter cell receives a copy of every chromosome.
Mitosis is usually accompanied by cytokinesis, or cytoplasmic division to produce two daughter cells.
Mitosis, therefore, maintains the chromosome number and generates new cells for the growth and
maintenance of an organism. In the adult organism, mitosis plays a role in cell replacement, wound healing
and tumour formation. Mitosis can take place in either haploid or diploid cells. Haploid mitotic cells are
found in fungi, plant gametophytes, and a few animals (including male bees known as drones).
Mitosis, although a continuous process, is conventionally divided into five stages: prophase,
prometaphase, metaphase, anaphase and telophase. (Greek: pro means before; meta means middle; ana
means back; telo means end).

Prophase:
Prophase is usually the longest mitotic phase. During the prophase, progressive coiling or condensation and
folding of chromosomes begin and they become visible as thread-like structures. During early prophase, the
two chromatids are twisted about each other in relational or plectonemic coils. Because the chromosome was
duplicated in the S phase, each chromosome possesses two chromatids attached at the centromere. A
structure known as the centrosome duplicates itself to form two daughter centrosomes that migrate to
opposite ends of the cell. The centrosomes organise the production of microtubules that form the spindle
fibres that constitute the mitotic spindle; this is a bipolar structure composed of microtubules and associated
proteins. The nuclear membrane breaks down to form a number of small vesicles and the nucleolus
disintegrates.

Molecular mechanism of chromosome condensation

Cohesins: During replication, the duplicated DNA molecules, called sister chromatids, become linked to
each other by a protein complex called cohesin, which are deposited along the length of each sister
chromatid. Cohesin is a member of the SMC, or structural maintenance of chromosomes, family of
proteins. SMC proteins are DNA-binding proteins that affect chromosome architectures; indeed, cells that
lack SMC proteins show a variety of defects in chromosome stability or chromosome behavior.
Condensin: Activated M-Cdk phosphorylates condensin, a large protein complex that contains SMC
protein. It is a long dimeric protein molecule hinged at the center with a globular domain at each end that
bind to DNA and hydrolyze ATP. When added to purified DNA, the condensin uses energy of ATP
hydrolysis to make a right handed loop. One molecule may be present for every 10000 nucleotides of mitotic
DNA and form a structural framework by forming intramolecular crosslinking to coil DNA.
Both Cohesins and condensins are structurally related and they work together.
Plectonemic Coiling: In plectonemic coiling, the sister chromatids are intertwined around each other so that
they cannot be separated from each other without rotation; this type of coiling occurs in prophase of mitosis.
Paranemic coiling: There is another type of coiling called paranemic coiling; in this case, the sister
chromatids are not twisted round each other but the coils of one sister chromatid are slipped into those of the
other so that they can be easily separated without rotation. Such coiling occurs in the prophase of meiosis.

Fig. The types of coiling between sister

chromatids.
A. In paranemic coiling (meiotic prophase) the
chromosomal subunits are not twisted around each
other and are freely separable.
B. In plectonemic coiling (initial prophase) the
chromosomal subunits are interwine.

Metaphase may be divided into: (i) Prometaphase, and (ii) Metaphase.

Prometaphase:
The dissolution of the nuclear envelope marks the start of the second phase of mitosis, prometaphase,
during which mitotic spindle assembly is completed and the chromosomes are moved into position at the
center of the cell. Spindle microtubules, which until now have been outside the nucleus, enter the nuclear
region. The ends of certain microtubules make contact with the chromosomes. For each chromosome, a
microtubule from one of the centrosomes anchors to the kinetochore of one of the sister chromatids; a
microtubule from the opposite centrosome then attaches to the other sister chromatid, and so the
chromosome is anchored to both of the centrosomes (chromosome orientation). The microtubules lengthen
and shorten, pushing and pulling the chromosomes about. Some microtubules extend from each centrosome
toward the centre of the spindle but do not attach to a chromosome. The chromosomes of a prometaphase
cell are moved by a process called congression toward the center of the mitotic spindle, midway between
the poles. The forces required for chromosome movements during prometaphase are generated by motor
proteins associated with both the kinetochores and arms of the chromosomes

Metaphase:
During metaphase, the chromosomes become arranged in a single plane, the metaphase plate, between the
two centrosomes. The centrosomes, now at opposite ends of the cell with microtubules radiating outward
and meeting in the middle of the cell, center at the spindle poles. A spindle-assembly checkpoint ensures
that each chromosome is aligned on the metaphase plate and attached to spindle fibers from opposite poles.
The passage of a cell through the spindle-assembly checkpoint depends on tension generated at the
kinetochore as the two conjoined chromatids are pulled in opposite directions by the spindle fibers.
This tension is required for the cell to pass through the spindle-assembly checkpoint. If a microtubule
attaches to one chromatid but not to the other, no tension is generated and the cell is unable to progress to
the next stage of the cell cycle. The spindle-assembly checkpoint is able to detect even a single pair of
chromosomes that are not properly attached to microtubules. The importance of this checkpoint is illustrated
by cells that are defective in their spindle-assembly checkpoint; these cells often end up with abnormal
numbers of chromosomes. Chromosomes in the metaphase stage are in the most condensed form.

In the beginning of metaphase, specialized protein complexes called kinetochores mature on each
centromere and attach to some of the spindle microtubules which are then called kinetochore microtubules.
The kinetochore microtubules align the chromosomes in one plane halfway between the spindle poles.
Each chromosome is held in tension at the metaphase plate by the paired kinetochore and their associated
microtubules, which are attached to opposite poles of the spindle.
Assembly of the metaphase spindle requires two types of events: Attachment of spindle microtubules to the
poles and captured the chromosomes by kinetochore microtubules. A kinetochore contacts the side of a
microtubule and then slides along the microtubule to the (+) end in a process that may involve kinesins on
the kinetochore. The kinetochore caps the (+) end of the microtubule. A combination of microtubule motor
proteins at the kinetochore and microtubule dynamics at the (+) end of kinetochore microtubules is thought
to position the chromosomes equally between the two spindle poles.

Anaphase:
It is the shortest stage of mitosis. During Anaphase an enzyme called separase degrades the multiprotien
complex called cohesins which held together the sister chromatids at their centromeres. The centromeres
divide, and the sister chromatids of each chromosome are pulled apart or 'disjoin' - and move to the opposite
ends of the cell; the kinetochores are pulled by kinetochore spindle fibres and are assembled at the
centrosomes. The separated sister chromatids are now referred to as daughter chromosomes. The
centromeres lead the way during chromosome movement at anaphase indicating that the chromosomes are
being pulled by the microtubules attached to them. The two arms of each chromatid drag behind forming
different shapes such as, V, J or rod, depending on the position of the centromere on the chromosome.
Simultaneous with the movement of chromosomes towards poles, the mitotic spindle also moves away from
each other. Thus both the types of movement are responsible for the separation of the two sets of
chromosomes from each other

Anaphase can be divided into two distinct stages anaphase A and anaphase B (early and late anaphases);
anaphase A is characterized by shortening of kinetochore spindle fibres which pulls the chromosome
towards the pole. On the other hand, during anaphase B the two poles move farther apart. It happens as a
result of spindle elongation which occurs due to sliding of polar microtubules past one another and pulling
forces exerted by astral microtubules.
Telophase:
When the chromosomes reach the opposite poles of the spindle, telophase is considered to begin. The
nuclear membrane re-forms around each set of chromosomes, producing two separate nuclei within the cell.
The chromosomes relax and lengthen, once again disappearing from view. In many cells, division of the
cytoplasm (cytokinesis) is simultaneous with telophase. The condensed chromatin expands once more, the
nucleoli which had disappeared at prophase begin to reappear, and mitosis is at an end.

Cytokinesis:
In animal cells, electron dense material condenses in the equatorial region of spindle at mid-anaphase, and
forms layer called “mid body”. During telophase, the microtubules embedded in the mid-body remain intact.
There occurs the in-folding of plasma membrane which causes a slight depression of a “cleavage furrow”
in the surface around the cell. Then a band of microfilaments called “contractile ring” appears below the
cleavage furrow in the cytoplasm. The microfilaments are responsible for creating the tension that cleaves
the cell into two daughter cells.
As the anaphase ends in plant cells, a layer of membrane vesicles is formed across the equatorial region of
the spindle. This structure is known as “phragmoplast”; it continues to grow outward and extends across
the wall. The phragmoplast vesicles fuse to form a double layered membrane sheet or “cell plate” dividing
the cell into two parts. Then the cell wall is formed by the accumulation of cell wall material between the
two membranes of the cell plate. After sufficient thickness, the cell wall splits down in the middle to
produce two cells that have intact plasma membranes and walls.
Thus the mechanism of cytokinesis in animal cells is different from that in plant cells. In animal cells, in-
folding of plasma membrane extends from outside of the cell towards the inner side, while in plant cells, the
cytokinesis starts from inside the cell and extends towards the periphery.
The distribution of cell organelles other than chromosomes, e.g., mitochondria, chloroplasts, endoplasmic
reticulum, ribosomes and microtubules etc. to the two daughter cells not necessarily equal. So long as the
two cells receive the minimum number of each of the granules, the shortage is made up by the production of
additional organelles during the next cell cycle.
Significance of Mitosis:

 Mitosis is an equational division.

 It is the division through which daughter cells that are identical are produced.
 The daughter cells have the same amount and type of genetic constitution as that of the parent cell.
 Mitosis division is responsible for growth and development of a single-celled zygote into a
multicellular organism.
 The chromosome number remains the same in the cells produced by this division.
 The daughter cells have the same characters as those of the parent cell.
 Mitosis division helps in maintaining the proper size.
 Mitosis also helps in restoring wear and tear in body tissues, replacing damaged or lost part, healing
wounds and regeneration of detached parts.
 This method of multiplication is seen in unicellular organisms.
 Mitotic division of cell is unchecked and it may result in uncontrolled growth of cells leading to
cancer or tumor.