CELL DIVISION AND

CELL CYCLE REGULATION

Arief Budi Yulianti

Department of Medical Biology and Histology
Faculty of Medicine - UNISBA
 Introduction

 Cellular proliferation is essential for normal

growth and development
 During embryogenesis, the cell division is very
important
 Different eukaryotic cell can grow and divide
quite different rates.
 Yeast cells can divide every 120 minutes
Animal cells take 10-20 hours to double in

number.

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Introduction

 Many cells in adults such as nerve cells,

muscle cells do not divide at all.
 In the experiment the conclusion is that
the
eukaryotic cell cycle consists of an M
(mitotic)
phase, a G1 phase (the first gap), the S
(DNA
synthesis) phase, a G2 phase (the second
gap)
and back to M.
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Type of Cell division

Amitosis  Prokaryote
Mitosis  eukaryote 
somatic cells
Meiosis  eukaryote 
germ cells
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Amitosis/Binary fission

 In prokaryote
 Cell division do not have step
 No formation of spindle
 Asexual reproduction
 Process :
 DNA replication  the copy attach in
different part of cell membrane

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 Mitosis
The process of mitosis ensures that when a
somatic cell divides in two, each resulting cell is
still 2n.
They are conventionally divided into four
sub-stages: prophase, metaphase, anaphase and
telophase.

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The beginning of mitotic cell division is the
appearance of the chromosomes.
During cell division the microtubules are important in
directing chromosome movement.
Microtubules comprise the tracks along which the
chromosomes move.
The centrioles also play a key role in
organizing the network of microtubules.
Centriole is a small cylindrical particle.
Centrioles are constructed of microtubules. They
duplicate during interphase. 9
 Prophase

During prophase and metaphase, a

chromosome consists of two coil filaments, the
chromatides held together by the centromere.
Each chromatid contains one of the two new
daughter DNA molecules produces in the S
phase of the cell cycle.
The two centrioles begin to move apart and
the microtubules forming aster.

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This radiating microtubule together with
associated proteins are called the spindle.
Other mictrotubule connect the centrioles with
the kinetochores.
Kinetochores is a plate like structure lying
within the centromere
By the end of prophase the nuclear membrane
has become invisible in the light microscope
the nuclear membrane breaks down into small,
flattened membrane vesicles.

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 Metaphase
•.During metaphase the chromatids migrate to the equatorial
plane of the cell.
•The chromosome are aligned at the equator. .
•In this phase, the morphology of the chromosomes are
usually studied.
•The mitotic apparatus at metaphase.
- Astral microtubules; forms aster.
- Kinetochore microtubule attach to
chromosome
- Polar microtubules do not interact with
chromosome.

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 Anaphase
This phase is marked by separation of the two sister
chromatid at their centromeres.
The kinetochores attached to each member of the
chromatid pair, now independent chromosome.
- Chromosome migrate along microtubule to
opposite poles of the cell by shortening of
kinetochore microtubules.
- The sparation happens simultaneously
- The two poles move further apart bringing the
chromosomes

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 Telophase
 In telophase the chromosome start to uncoil
and become less condense.
 Nuclear membrane vesicle are seen joining
together to become two new nuclear
membrane. The new nuclear membrane
surrounding the two set of daughter
chromosome.
Simultaneously there is division of the cell
cytoplasm  pinched formation cleavage furrow

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 Cytokinesis

• Pinched formation was beginning shortly after sister

chromatid sparatted
• Contractile ring  myosin II and actin filament  cleavage
furrow

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Meiosis
Meiosis is the form of cell division in which haploid
germ cells are produced from diploid cells.
Meiosis, is the division that give rises two gametes,
sperm and egg cell, in higher plants and animals.
A premeiotic cells is diploid, contains two of each
morphologic type of chromosome.
The two chromosomes of each type are descended from
different parents, so they are homologous.
Homologous means their genes are similar but are
usually not identical.
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In meisois, one round of DNA replication, make the
cell 2n, is follwed by two separated cell division,
yielding 4 haploid (1n cell).
Meiosis consists of first and second meiotic division.
There is an interphase between first and second
meiosis.
During the first meiotic division each chromosome
aligns at the cell equator paired with its partner.
No division of centromeres occures.
The sister chromatids remain together
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One homolog is randomly selected to travel to one
daughter cell, the other homolog goes to the other cell.
Because one homologous chromosome come from the
egg and the other from a sperm, the parental
characteristics are reassorted randomly into each
daughter cells.
In the second meiotic division the centromere devide as
in mitosis.
One sister chromatid of each type of chromosome is
apportioned in to haploid daughter cell.
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 Meiosis I and II are each divided into four phases: prophase, metaphase,
anaphase, and telophase.
 The first meiotic prophase is a complex process separated into five
stages.
 Leptotene  the chromosomes coil and contract each consists of two
chromatids.
 Zygotene synapsis: pairs of homologous chromosomes come into point-to-
point contact along their length (bivalent). The X and Y chromosomes synapse
only at the ends of the short arms.
 Pachytene the chromosomes thicken. The bivalent is now a tetrad of four
chromatids. Crossing over occurs  Chromosome combination, parental and
new combination
 Diplotene  bivalent separate except for X-shaped chiasmata where
crossover has occurred. In the female, this stage (called dictyotene) is
prolonged; the oocyte remains in this stage from late fetal life until the time of
ovulation.
 Diakinesis, the chiasmata move to the ends of the chromosomes.

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Figure 10.6 Meiosis I
The exchange of color
between non sister
chromatids represents
crossing-over

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Figure 10.7 Meiosis II
During Meiosis II,
daughter chromosomes
consisting of one
chromatid each move to
the poles. Following
meiosis II, there are 4
haploids daughter cells.

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Figure 10.8
Homologopus
chromosomes
These chromosomes are
duplicated and each one
is composed of two
chromatids. The sister
chromatids contain the
exact same genes; the
non sister chromatids
contain only genes for the
same traits, like type of
hair, color of eyes.

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The segregation of homolog chromosomes in
meiosis is random, the maternal and paternal
members of its pair segregate independently.
Before the first meiotic division the chromosomes of
each homologous pair align with each other called
synapsis.
At this time recombination between chromatids can
occur.
The swapping of materials between the chromosome
is called crossing over.
Crossing over is the source of new combinatioan of
genes in interbreeding population. 26
Meiosis KM 27
Meiosis KM 28
Meiosis KM 29
Animation

Meiosis KM
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Cell cycle regulation

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CELL CYCLE
 The cell cycle is defined as a period from
time a cell comes into existence until the cell
divides to two daughter cells

 In culture, the human cell cycle last for 20 –

24 hours. In the human body the cell cycle
can be shorter or it can be much longer.

 Liver hepatocytes to divide only once or

twice a year.

 Mitosis or M phase occur within 1 to 2 hours,

the remainder of the cell cycle is known as
the interphase.
 Cell cycle divided into 4 phases or stages; the
S phase, G2 phase, M phase and G1 phase.

The length of time occupied by S, G2 and M

phase is relatively constant. Therefore the
length of the cell cycle is confined by the
duration of the G1 phase.
 In some cell, G1phase is nonexistent means
the cell divide rapidly. In other cell, the
G1phase may be so long that the cell stop
cycling. In this case the G1 phase is called Go
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PHASES OF THE CELL CYCLE.
The S (synthesis) phase is the period of the DNA
duplication. The sister chromatids are produced.
The G2 ( Gap 2) phase is the period between S
phase and M phase. During the G2 the cell is
preparing for mitosis. The centrioles migrate to the
opposite poles.
 M (mitosis) phase is the period when the cell do
the cell division.
 G1 (Gap1) phase is a period of celluler growth.
 Duration of the G1 determined the length of the
cell cycle
 The long of G1 period is 30 –40 % of the time cell
cycle.

 There are syntesis of RNA ( transcription ) and syntesis

of protein ( translation ), make a new protoplasma .

 Event duplication of genetic materials, cytoplasmic

materials and organells.

 Enlarge of nucleus and cytoplasma.

 The long of S phase is 30 – 40 % of the time cell

cycle.
 There is occur of syntesis DNA ( replication ), make a
new genetic materials which the same arrangement
DNA.

The long of G2 period is 10 – 20 % of time cell cycle

- Preparation splitting of cytoplasma.
- Finishing the sintesize of materials in the G1 period
until all of the cytoplasmic materials and organells was
diploid.

 -G2 period soon followed the mitosis.

REGULATION OF THE CELL CYCLE.

 The cell cycle regulators are two families of protein:

the cyclins and cyclin dependent kinases (Cdks).

 Cyclins are cyclically synthesized and degraded in

each cell cycle. The cdk enzymes are inactive until
they bind to the specific cyclin.
Cyclins

 Go  Cyclin C
 G1 D cyclin and E cyclin
 S E cyclin and A cyclin
 G2  A Cyclin
 M B cyclin

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Cyclin dependent Kinases
(Cdks)
Go  cdk3
G1 Cdk 4, cdk2, cdk6
SCdk 2
G2  cdk2, cdk1
MCdk 1
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Cell Cycle Clock: Cyclins and Cyclin-
Dependent Kinases
Cyclin fluctuates cyclically within
the cell.

Cyclin–dependent kinases (Cdks)

such as MPF must be attached to
cyclin to be active (MPF = mitosis
promoting factor)

Activity of Cdks rise and fall with

changes in cyclin concentration.

MPF complex initiates mitosis by

phosphorylating a variety of
proteins.

MPF switches itself off by initiating

a process that breaks down cyclin.
Group of cyclin
 G1/S cyclins – essential for the control of the cell cycle at
the  G1/S transition
 Cyclin A/ CDK2  active in S phase.
 Cyclin D/ CDK4, Cyclin D / CDK6, and Cyclin E/ CDK2 
regulates transition from G1 to S phase.
 G2/M cyclins – essential for the control of the cell cycle at
the  G2/M transition  mitosis.
 G2/M cyclins accumulate steadily during G2 and are
abruptly destroyed as cells exit from mitosis at the end
of the M-phase
 Cyclin B/ CDK1– regulates progression from G2 to M
phase.

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 Variation in Cell Cycle Cyclins
Cyclin-dependent kinases

Cdk4 Cdk2 Cdk1

cyclins D E A B(A)

M G1 S G2 M G1

Start

Cell cycle phases

Check Points
 DNA damage checkpoints.
 G1 checkpoint/Restriction point
 Damage to DNA before the cell enters S phase inhibits
the action of Cdk2 cell cycle stop until repair  if
can’t repair apoptosis
 G2 checkpoint
 Damage to DNA after S phase  inhibits the action
of Cdk1  preventing the cell from proceeding from
G2 to mitosis.
 If replication stops at any point on the DNA  cell cycle is
halted
 M checkpoint
 Mitotic spindle checkpoint
 Metaphase - anaphase 47
 Environmental regulation of the cell cycle

 Growth factors are polypeptide group, will regulate the

cellular proliferation
 Each growth factors has specific target cells and tissues.
The receptor is found in membrane of the target cells.
 Binding of the receptor to the growth factor will stimulate
a cell to exit from the quisscent G0 phase of the cell cycle
and enter to G1 phase.
 If the growth factors are sufficient in the environment, the
cell will continue to cycle.
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 Cell Cycle Regulation
Cell Cycle analogy to washer machine control

The cell cycle is driven by an internal clock regulated at certain

checkpoints by both external (ex: faucets) and internal (ex:
sensor) controls.
Major Checkpoints of the Cell Cycle Control System