Download Main text Introduction Mitosis (Gk. Mitos – warp thread or fiber and

Main text
Introduction
Mitosis (Gk. Mitos – warp thread or fiber and osis –
act, process) is a type of equational division in which
chromosomes replicate and become equally distributed
among the two daughter nuclei.
Mitosis was first
observed in plant cells by Strasburger in 1870 and in
animal cells by Boveri and W. Flemming in 1879. The
term ‘mitosis’ was introduced by Flemming in 1882 as
chromatin of the cell nucleus appears as long threads in
the first stage.
It is the usual method of cell division in all eukaryotic
organisms. It is characterized typically by resolving the
chromatin of the nucleus into a threadlike form which
condenses into chromosomes, each of which separates
longitudinally into two parts called chromatids, each of
which is retained in each of two new cells resulting from
the original cell.
The development of an individual from zygote to
adult stage takes through mitotic cell divisions and it is
the most common method of division which brings about
growth
in
multicellular
organisms,
and
increase
in
population of unicellular organisms. Although growth also
takes place through increase in cell size, but when cell
size increases, surface area of cell does not increase in
the same proportion as the cell volume. Therefore, cell
division helps in growth also by way of increasing surface
area of the cell. Thus, mitosis is a necessity for the
maintenance and perpetuation of life.
One of the basic requirements of cell division meant
for growth would be that it should give rise to two
daughter cells, which should resemble each other and
also the parent cell qualitatively and quantitatively.
Since a cell also has to maintain continuity from one
generation to another, and since the heredity material
within the chromosomes has to copy itself most faithfully,
a cell has to divide in growing tissue and elsewhere in
such a manner that the two daughter cells are similar to
each other and resemble the parent cell from which these
were produced. However, in divisions taking place in sex
cells, the daughter cells may differ from one another and
also from parent cells, but they would still have most of
the essential features in common. The basic outline of
cell division in all the living organisms is almost the same
which for the sake of convenience of description is
divided into different phases constituting what is called as
the cell cycle.
Cell cycle
Cell cycle can broadly be divided into interphase and
mitosis.
In the interphase, the cell prepares materially
for the division and the mitosis (M phase) is the main cell
division phase, where the cell actually divides into two.
Interphase: Preparation for Mitosis
Interphase is the phase of the cell-cycle in which the
cell spends the majority of its time and performs the
majority of its purposes, including preparation for cell
division. In this preparation, the cell increases its size
and makes a copy of its DNA, the centrioles divide, and
proteins
are
actively
produced.
Interphase
is
also
considered to be the 'living' phase of the cell, in which
the cell obtains nutrients, grows, reads its DNA, and
conducts other "normal" cell functions. The majority of
eukaryotic cells spend most of their time in interphase.
Interphase does not describe a cell that is merely resting
but is rather an active preparation for cell division. The
interphase is divided into following 3 sub stages:
 G1 (Growth 1 or Gap 1) phase
It is the phase, in which the cell grows and functions
normally. During this time, much protein synthesis occurs
and the cell grows (to about double its original size) more organelles are produced, increasing the volume of
the cytoplasm. The DNA in a G1 diploid eukaryotic cell is
2N, meaning that there are two sets of chromosomes
present in the cell. Haploid organisms, such as some
yeast will be 1n and thus have only one copy of each
chromosome present. A cell may pause in the G1 phase
before entering the S phase and enter a state of
dormancy called the G0 phase (discussed latter). Most
mammalian cells of nerve and muscle tissue systems do
this. In order to divide, the cell re-enters the cycle in ‘S’
phase. There is a "restriction point" present at the end of
G1 phase. This point is a series of safeguards to ensure
that the DNA is intact and no repairment is required, and
that the cell is functioning normally. Functionally, the
safeguards exist as proteins known as cyclin-dependent
kinases (CDKs), called as S-phase promoting factor (SPF)
or G1/S phase checkpoint and will be discussed latter.
The G1 CDK proteins activate the transcription factors for
a variety of genes. These include genes which are
responsible for DNA synthesis proteins and S phase CDK
proteins.
 S-Phase (Synthetic phase)
During this phase, the synthesis of DNA (via semiconservative replication) and other preparations for main
cell division take place. The DNA is the ‘brain’ of the cell;
hence the cell will need to copy its DNA faithfully in order
to pass it on to two daughter cells. At the beginning of
the S stage, each chromosome is composed of one coiled
DNA double helix molecule. The enzyme DNA helicase
splits the DNA double helix and DNA polymerase start,
attaching complementary base pairs to the DNA strand,
making two new semi-conservative strands. At the end of
this stage, each chromosome has two identical DNA
double helix molecules and, therefore, is composed of
two
sister chromatids
which remain joined
at the
centromere. During S phase, the centrosome is also
duplicated. The end result is the duplication of genetic
material in the cell, which will eventually be divided into
two. Damage to DNA often takes place during this phase,
and DNA repair is initiated following the completion of
replication. Incomplete or poor DNA repair may flag cell
cycle checkpoints, which halts the cell cycle. However,
after the cell has completed this phase, it is very likely
that the cell will continue on to complete the cell cycle.
 G2 (Growth 2 or Gap 2) Phase
It is the phase in which cell undergoes a period of
rapid growth in preparation for mitosis. It is the last
stage of cell cycle up to which nucleus is well defined
bounded by nuclear membrane and with nucleolus.
Chromosomes although replicated are in the form
loosely packed chromatin fibers. As in G1 phase, at the
end of this phase too is a control check point called
G2/M- checkpoint.
 G0 Phase
As discussed above in G1 phase, some cells that do not
divide often or ever, enter a stage called G0 (Gap zero),
which is either a stage separate from interphase or an
extended G1 phase, which follows the restriction point, a
cell cycle checkpoint found at the end of G1.
In this phase, cells exist in a quiescent state. This is
sometimes referred to as a "post-mitotic" state, since
cells in G0 phase are in a non-dividing phase outside of
the cell cycle. Some types of cells, such as nerve and
heart muscle cells, become post-mitotic when they reach
maturity (i.e., when they are terminally differentiated)
but continue to perform their main functions for the rest
of the organism's life. Multinucleated muscle cells that do
not undergo cytokinesis are also often considered to be in
the G0 stage. On occasions, a distinction in terms is made
between a G0 cell and a 'post-mitotic' cell (e.g., heart
muscle cells and neurons), which will never enter the G1
phase, whereas other G0 cells may enter.
Cells enter the G0 phase from a cell cycle checkpoint
in the G1 phase, such as the ‘Restriction point’ (animal
cells) or the ‘START’ point (yeast). This usually occurs in
response to lack of growth factors or nutrients. During
the G0 phase, the cell cycle machinery is dismantled and
cyclins and cyclin-dependent kinases disappear. Cells
then remain in the G0 phase until there is a reason for
them to divide. Some cell types in mature organisms,
such as parenchymal cells of the liver and kidney, enter
the G0 phase semi-permanently and can be induced to
begin
dividing
again
only
under
very
specific
circumstances. Other types of cells, such as epithelial
cells, continue to divide throughout an organism's life
and rarely enter G0.
Although many cells in the G0
phase
may
die
along
with
the
organism, not all cells that enter the
G0 phase are destined to die; this is
often simply a consequence of the
cell's lacking any stimulation to reenter in the cell cycle.
The term "post-mitotic" is sometimes used to refer
not only to quiescent cells (like those in G0) but also to
senescent cells. Cellular senescence is distinct because it
is a state that occurs in response to DNA damage or
degradation that would make a cell's progeny nonviable.
Senescence
then,
unlike
quiescence,
is
often
a
biochemical alternative to the self-destruction of such a
damaged cell by apoptosis. At any given time, most of
the cells in an animal’s body are in G0 phase; however
some cells among them, like liver cells can resume G1
phase in response to factors released during injury.
Cell cycle duration
The duration of various phase of cell cycle vary from
organism to organism and even in different tissues of the
same organism. Cells in growing animal embryos can
complete their cell cycle in less than 20 minutes; the
shortest known animal nuclear division cycle occurs in
fruit fly (Drosophila) embryos (8 minutes). Most cells of
adult mammals spend about 20 hours in interphase, this
account for about 90% of the total time involved in cell
division. However generally if we assume the cell cycle of
a particular cell to be of 24 hours, more than 23 hours of
it will be consumed in interphase and only less than one
hour will it spent in Mitosis or M phase. For example
mouse L cells dividing for every twenty four hours spent
12 hours in G1 phase, 6-8 hours in S phase; 3-6 hours in
G2 phase and only 1 hour in M phase; similarly cells of
Vicia faba (Broad beans) spent 12 hours in G1 Phase, 6
hours in S phase, 12 hours in G2 phase and 1 hour in M
phase. Some cells such as certain cells in human liver
have cell cycles lasting more than a year.
Mitosis or M-Phase
The onset of M-phase is allowed by the formation of
the mitotic cyclin-Cdk complex known as M phase
promoting factor that occurs as a cell cycle regulatory
mechanism in the G2 phase.
The
primary
result
of
mitosis is the transferring of the
parent cell's genome into two
daughter cells. The genome is
composed
of
a
number
chromosomes-complexes
of
of
tightly-coiled DNA that contain
genetic
information
vital
for
proper cell function. The mitosis
or M phase of the cell cycle although a continuous
process is for the sake of convenience and understanding
divided into following sub-phases.
Preprophase
In plant cells only, prophase is preceded by a preprophase 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 being organized into
a spindle by the chromosomes themselves, after the
nuclear membrane breaks down. The preprophase band
disappears
during
nuclear
envelope
dissolution
and
spindle formation in prometaphase.
Prophase
At the beginning of the prophase the nucleus of the
cell
becomes
spheroid,
viscosity
of
the
cytoplasm
increases and the chromatin fibers start condensing and
thinning
to
Chromosomes
take
the
become
shape
coiled,
of
chromosomes.
shortened
and
more
distinct as the prophase progresses. This shortening and
thickening of chromosomes is due to two reasons: (1)
coming together of scaffolding or axial proteins and (2)
lateral looping and coiling of chromatin fibers which is
assisted by a category of proteins called condensins.
At the early prophase the
chromosomes
are
evenly
distributed in the nucleus. As the
prophase
progresses
chromosomes
begin
the
to
align
themselves to the periphery of the
nucleus creating a clear central
area. Chromosomes continue shortening and thickening
to assume the characteristic shape and size, which is
necessary for their equitable distribution latter.
An important and
characteristic
feature of
the
prophase is longitudinal splitting of the each chromosome
into two sister chromatids which remain attached to each
other
only
at
centromere.
In
the
late
prophase
chromatids at the centromere will get attached with the
spindle fibers with the help of kinetochore. The nucleolus
and nuclear membrane (with some exceptions) start
disappearing. The centrosomes which are the organizing
centre of microtubules begin to separate to opposite
poles of the cell in the form of asters (centrioles and
microtubule astral rays). However spindle poles are
organized
without asters
in plant cells
which lack
centrioles.
Prometaphase
The major event marking the cell’s entry to
prometaphase is the breakdown of the nuclear
envelope into small vesicles. Kinetochores (a
proteinous structure at the centromere region of
the sister chromatids) become fully matured on
the centromeres of the chromosomes. Distinction
between cytoplasm and nucleoplasm fades and
the organelles like Endoplasmic Reticulum (ER) and Golgi
apparatus disorganize. The segregation of the replicated
chromosomes is brought about by a complex cytoskeltal
machine with many moving parts- the mitotic spindle. It
is constructed from microtubules (tubulin dimers) and
their associated proteins, which both pull the daughter
chromosomes towards the poles of the spindle and move
the poles apart.
Both the assembly and the function of the mitotic
spindle
depend
on
microtubule-dependent
motor
proteins. These proteins belong to two families- the
kinesin-related proteins, which usually move toward the
plus end of the microtubules, and the dyneins, which
move towards the minus end. In the mitotic spindle,
motor proteins operate at or near the ends of the
microtubules.
These
ends
are
not
only
sites
of
microtubule assembly and disassembly; they are also
sites of force production. The assembly and dynamics of
the mitotic spindle rely on the shifting balance between
opposing
motor
plus-end-
proteins.
directed
Microtubules
and
minus-end-directed
emerging
from
the
centrosomes at the poles of the spindle reach the
chromosomes.
The attachment of the chromosomes with the spindle
is a dynamic process. It seems to involve a search and
capture mechanism, in which microtubules radiated from
each of the rapidly separating centrosomes grow outside
toward the chromosomes. Microtubules that attach to a
centromere become stabilized, so that they no longer
undergo catastrophes. They eventually end up attached
end-on at the kinetochore (a complex protein machine
that assembles onto the highly condensed DNA at the
centromere
during
late
prophase).
The
end-on
attachment to the kinetochore is through the plus end of
the microtubules, which is now called a kinetochore
microtubule.
In the spindle, some microtubules extend from one
pole to the centre of the cell, where
their ends overlap with the ends of
other microtubules that extend from
the opposite end of the spindle. The
two sets together, overlapping in the
centre
form
a
large
framework.
Other microtubules run from a pole
to a centromere. Each end of the
spindle is attached to one of the two faces of the
centromere at kinetochore on each chromosome. About
15 to 35 microtubules attach to each kinetochore.
The role of prometaphase is completed when all of
the kinetochore microtubules have attached to their
kinetochores,
unattached
upon
which
kinetochore,
metaphase
and
thus
a
begins.
An
non-aligned
chromosome, even when most of the other chromosomes
have lined up, will trigger the spindle checkpoint signal.
This prevents premature progression into anaphase by
inhibiting
the
anaphase-promoting
complex
until all
kinetochores are attached and all the chromosomes
aligned.
Metaphase
Once
the
chromosomes
get
captured
by
the
microtubules of the spindle, the microtubules push and
pull on the chromosomes, gradually aligning them to the
cell centre or spindle equator forming what is called as
Metaphase plate. This alignment is due to the counterbalance of the pulling powers generated by opposing
kinetochores
Mitotic cells usually spend about half of M phase in
metaphase,
with
the
chromosomes
aligned
on
the
metaphase plate, jostling about, awaiting the signal that
induces sister chromatids to separate to begin anaphase.
Treatment with drugs that destabilize microtubules, such
as colchicine or vinblastine arrests mitosis for hours or
even days. This observation led to the identification of a
spindle attachment check-point which is activated by the
drug treatment and arrests progress in mitosis. The
checkpoint mechanism is used by the cell cycle control
system to ensure that the cells do not enter anaphase
until all chromosomes are attached to both poles of the
spindle. If one of the protein components of the
checkpoint mechanism is inactivated by mutation or by
an
intracellular
injection
of
antibodies
against
the
component, the cells initiate anaphase permanently.
The spindle attachment checkpoint monitors the
attachment of the chromosomes to the mitotic spindle. It
is thought to detect either unattached kinetochores or
kinetochores that are not under the tension that results
from
bipolar
attachment.
In
either
case
attached
kinetochore emit a signal that delays anaphase until they
all are properly attached to the spindle. Drugs that
destabilize microtubules prevent such attachment and
therefore maintain the signal and delay the anaphase.
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 ανα meaning “up,” “against,” “back,” or “re-”).
Entrance
into
anaphase
is
triggered
by
the
inactivation of M phase-promoting factor that follows
mitotic
cyclin
degradation.
During
anaphase,
the
kinetochore
microtubules
retract,
increasing
the
separation of the sister chromatids as they are moved
further toward the opposite spindle
poles.
Anaphase can be subdivided
into two distinct phases. In the
first phase, called Anaphase A,
chromosomes move pole ward,
away from the metaphase plate
with the retraction of the microtubules. This movement
occurs at approximately 2 micrometers per minute (the
entire
length
of
a
cell
is
between
10
and
30
micrometers). In the second phase, or Anaphase B, the
mitotic poles marked by the centrosomes themselves
separate by the elongation of a specific type of nonkinetochore microtubule, called a polar microtubule. The
extent of the separation of the poles varies from species
to species. The entire duration of anaphase is relatively
short, usually only lasting a few minutes. As if following a
neatly
choreographed
dance,
the
sister
chromatids
separate, rapidly moving toward the pole to which their
microtubule is attached. The cell appears "stretched" as
the spindle fibers slide past one another, elongating the
spindle apparatus and further separating the poles.
Shortening of the microtubules by removal of tubulin
units pulls the chromosomes closer and closer to the
pole. The movement of sister chromatids to opposite
sides of the cell completes the equal division and
distribution of genetic material.
Agents that inhibit microtubules depolymerization,
such as
deuterium oxide, also
inhibit chromosome
movement, where as those that speed depolymerization
such as low level of colchicines, speed movement. The
amount of energy necessary to move a chromosome
from the metaphase plate to the end of the spindle is
small;
just
20
ATP
molecules
are
sufficient.
Long
chromosomes may tangle somewhat, but microtubules
exert sufficient pull to untangle them and drag them to
the ends of the spindle. Because the spindle is shaped
like a football, as chromosomes on each side get closer to
the end, they are pulled together into a compact space.
Chromatids separate from each other with the breakdown
of the cohesion linkage the protein complex that binds
the sister chromatids at the metaphase plate.
This metaphase-to-anaphase transition is triggered
by the activation of the anaphase promoting complex
(APC) or cyclosome APC. The APC is a complex of several
proteins.
APC
cohesion.
directly
When
all
triggers
the
the
degradation
kinetochores
are
of
properly
attached with the microtubules in the metaphase, the
APC becomes active. The activated APC then targets
securin for degradation. Degradation of securin allows a
cysteine protease called separase to cleave chromosome
bound cohesion allowing anaphase onset.
Once this proteolytic complex is activated, it has at least
two crucial functions: (1) it cleaves and deactivates the
M-phase cyclin (M-cyclin) thereby inactivating M-Cdk;
and (2) it cleaves inhibitory securing, thereby activating
the separase. Separase then cleaves a subunit in the
cohesion complex to unglue the sister chromatids. The
sister chromatids immediately separate- and are now
called daughter chromosomes- and move to opposite
poles.
Telophase
In telophase (Gk telos-end, phase-stage), the spindle
apparatus disintegrate as the
microtubules are broken down
into tubulin monomers that can
be
used
to
construct
the
cytoskeletons of the daughter
cells.
Fragment
of
nuclear
envelope appear near around
each set of sister chromatids
which
can
chromosomes,
complete
now
be
connect
nuclear
called
with
envelope
each
other
around
and
each
form
set
of
chromosomes. The chromosomes again start uncoiling
into more loose threads of chromatin, which enable them
for gene expression. It is not known how new nuclear
pores are formed. Gradually, new nucleoli appear as the
ribosomal genes become active and produce ribosome
subunits. The spindle depolymerizes completely and
disappears. Most of the events in telophase are reversal
of those in prophase.
Cytokinesis
Cytokinesis, from the Greek cyto- (cell) and kinesis
(motion, movement) is the process in which the cell
actually divides into two. With the two nuclei already at
opposite poles of the cell, the cell cytoplasm separates,
and the cell pinches in the middle, ultimately leading to
cleavage.
Cytokinesis
is
often
mistakenly thought to be
the final part of telophase;
however, cytokinesis is a
separate
process
that
begins simultaneously with telophase. Cytokinesis is
technically not 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
develops
ring
where
the
metaphase plate used to be, pinching off the separated
nuclei. During different proliferative divisions, animal cell
cytokinesis begins shortly after the onset of sister
chromatid separation in the anaphase of mitosis. A
contractile ring, made up of myosin II and actin
filaments, assembles in the middle of the cell. Myosin II
uses the free energy released when ATP is hydrolyzed to
move along these actin filaments, constricting the cell
membrane
to
form
a
cleavage
furrow.
Continued
hydrolysis causes this cleavage furrow to move inwards.
Ingression continues until a so-called midbody structure
is formed and the process of abscission then physically
cleaves this midbody into two.
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 plant cell, due to the presence of a cell wall;
cytokinesis is significantly different from that in animal
cells. Rather than forming a contractile ring, plant cells
construct a cell plate in the middle of the cell. The Golgi
apparatus releases vesicles containing cell wall materials.
These vesicles fuse at the equatorial plane and form a
cell plate. The cell plate begins as a fusion tube network,
which then becomes a tubulo-vesicular network (TVN) as
more components are added. The TVN develops into a
tubular network, which then becomes a fenestrated sheet
which adheres to the existing plasma membrane.
Cell cycle control and checkpoints
Leland Hartwell (born 1939), of HCRC, USA, was
awarded noble prize in medical physiology in 2001for his
discoveries of a specific class of genes that control the
cell cycle. One of these genes called "start" was found to
have a central role in controlling the first step of each cell
cycle. Hartwell also introduced the concept "checkpoint",
a valuable aid to understanding the cell cycle.
We know that cell cycle involves the synthesis and
division of DNA- the genetic material of the cell, which
directly or indirectly controls all the activities and future
course of action of the new formed cells. Therefore it
becomes very important for the cell cycle to repair all the
possible errors which can occur during S phase in DNA
before the nuclear division so that the faulty
DNA can be prevented from proliferation. For
that matter, the cell has developed very efficient system
of controls in form of cell cycle checkpoints. These
checkpoints are also necessary because, the synthesis of
DNA
and
separation
of
chromatids
are
irreversible
processes and need to be examined before happening.
The cell cycle checkpoints put it on hold at specific points
so that the processes can be assayed for accuracy and
halted in case of any error. A cell uses three checkpoints
during the whole processes at specific points in the cell
cycle to access the accuracy and to integrate the external
and internal signals before its transition to next phase.
The passage through these checkpoints is controlled
by
cyclin
dependent
serine/threonine
kinases,
kinase
which
(CDK)
regulate
family
cell
of
cycle
progression through phosphorylation of proteins that
function at specific phases of the cell cycle. These kinase
were discovered by Paul Nurse at different phases of the
cell cycle and their activity is each dependent on
association with a member of the cyclin family of
regulatory sub-units. These kinases are therefore called
as cyclin dependent kinases or Cdks.
The checkpoints are discussed as below:
G1/S checkpoint: This is the first checkpoint where a
cell in response to surroundings can decide whether to
divide or not. The possible factors which govern this
checkpoint include growth factors, nutritional status of
the cell and the fitness of the genome. Poor nutritional
status, lack of growth factors and damaged DNA can halt
the cell cycle at this point. This checkpoint has been well
studied in yeast where it is being termed as ‘START’. In
animals it is termed as ‘restriction point’.
G2/M
checkpoint:
This
is
the
second
and
most
important checkpoint which is meant for assessment of
DNA which has been synthesized in S phase. This
checkpoint is commonly referred to as Mitosis Promoting
Factor (MPF). The G2 checkpoint provides an opportunity
for repair of damaged DNA if any, hence stopping the
proliferation of damaged cells therefore help to maintain
genomic
stability.
Passage
through
represents the commitment to mitosis.
this
checkpoint
Any substance
which damages DNA can cause the cycle to stop at this
point.
Spindle
checkpoint
at
late
metaphase:
this
checkpoint comes into action just before the partition of
two sets of chromosome destined
for
two
daughter
cells
at
metaphase. The second irreversible
step in cell cycle is the segregation
of chromatids during anaphase;
hence
the
Spindle
checkpoint
ensures that all the chromosomes are attached to spindle
fibers correctly before transition into anaphase.
Molecular mechanism of Cell cycle controls
The primary molecular mechanism of the cell cycle
control is due to the phosphorylation (addition of
Phosphate) and dephosphorylation (removal of
phosphate) of proteins. The enzymes which bring about
phosphorylation are called as kinases and those which
bring about dephosphorylation are called as
phosphatases. The phosphorylation of a protein can
activate or inactivate a protein depending upon the
protein. Similarly the protein inactivated by
phosphorylation can be activated by dephosphorylation
and vice versa. As discussed above the enzymes which
carryout phosphorylation of proteins are cyclin dependent
kinases (Cdks) which in combination bring about the
phosphorylation of a variety of cellular proteins thereby
controlling the different stage of the cell cycle. The most
important Cdk was isolated in fission yeast and was
named as cdc2. It has now become clear that the cdc2
kinase is controlled by phosphorylation, and a specific
cyclin associated with it. Phosphorylation of cdc2 at one
site activates it and phosphorylation at another site
deactivates it. Similarly cdc2 can combine with different
cyclins at different stages of cell cycle. Thus the signal to
start the cycle at one point comes with the combining of
cdc2 with one cyclin and the signal at another stage of
the cycle comes by joining of the cdc2 with another
cyclin. The exact molecular mechanisms of Cdk control
are still not well established.