CELL DIVISION

SUB TOPICS

8.1 Eukaryotic Chromosomes

8.2 Mitosis and Meiosis
8.3 Comparison of Mitosis and Meiosis
8.4 Cell Cycle
8.4.1 Regulation of Cell Cycle
8.5 Cancer

CELL DIVISION

LEARNING OBJECTIVES

At the end of this lesson, students should be able to:

✓ Describe the structure of eukaryotic chromosomes
✓ Define the terms: homologous chromosomes, haploid, diploid, somatic cells, genome, gametes,
chromatin, sister chromatids, centromere, kinetochore.
✓ List down the 5 phases of the cell cycle
✓ Briefly describe the cellular events that highlight each phase/stage of the cell cycle
✓ Compare the duration of the different phases of the cell cycle between different cell
types/tissues/organisms
✓ Describe the behavior of chromosomes during the different stages of mitosis and meiosis and the
associated behavior of the nuclear envelope, cell membrane and centrioles.
✓ Explain how mitosis differs between plant and animal cells.
✓ Describe the process of cytokinesis in animal and plant cells.
✓ Describe the components, functions and mechanism of the cell cycle control system.
✓ Explain how cancer is a result of uncontrolled cell division.
✓ List factors which may increase the chances of cancerous growth
✓ Define the terms: cancer, metastasis, oncogene, protoncogene,
✓ apoptasis, tumour suppressor gene and carcinogen.
✓ Explain and link cancer with the failure of the cell cycle control.
✓ List down the various type of tumours
✓ Explain the role of the p53 gene

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EUKARYOTIC CHROMOSOME

Fluorescence LM of a cultured newt lung cell in mitosis (early prometaphase). The nuclear
envelope has broken down, and the microtubules of the mitotic spindle (green) now interact with
the chromosomes (blue)

Figure 10-2 Nucleosomes

(a) A model for the structure of a nucleosome. Each nucleosome bead contains a set of eight histone
molecules, forming a protein core around which the double-stranded DNA winds. The DNA
surrounding the histones consists of 146 nucleotide pairs; another segment of DNA, about 60
nucleotide pairs long, links nucleosome beads.

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 Figure 10-2 Nucleosomes
(a) A model for the structure of a nucleosome. Each nucleosome bead contains a set of eight histone
molecules, forming a protein core around which the double-stranded DNA winds. The DNA
surrounding the histones consists of 146 nucleotide pairs; another segment of DNA, about 60
nucleotide pairs long, links nucleosome beads.

Figure 10-3 TEM of a mouse chromosome depleted of histones

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Notice how densely packed the DNA strands are, even though they have been released from the
histone proteins that organize them into tightly coiled structures.

Figure 10-4 Organization of a eukaryotic chromosome

Figure 10.4 shows how DNA is packaged into highly condensed metaphase chromosomes. First, DNA
is wrapped around histone proteins to form nucleosomes. Then, the nucleosomes are compacted
into chromatin fibers, which are coiled into looped domains. The looped domains are compacted,
ultimately forming chromosomes.

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MITOSIS
Chromosomes carry genetic information in eukaryotic cells.
Chromosomes are made from chromatin.
Chromatin is made from DNA.
During cell division, chromatin condense.
Eukaryotic chromosome is bounded to histones.
They will form a structure called Nucleosomes. Fig.10.2
Nucleosome consists of 8 histones that is wrapped by DNA.
Histones is also believed to play a role in gene expression.
Nucleosome prevents DNA from tangling.
The loops in chromatin is also held together by scaffolding proteins . Figure 10.3
There is also a type of proteins known as condensin that assist in chromosome compaction.
Condensin binds to DNA and wraps it into coiled loops that is compacted into a chromosome.

Every species has its unique chromosome numbers.

Below are a few examples of chromosomes I different species.

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CELL CYCLE AND MITOSIS
When cells reach a certain size, they either stop growing [Go] or divide.
Neurons, skeletal muscles and red blood cells do not divide once they mature.
Other cells undergo a sequence of activities required for growth and cell division.

CELL CYCLE is defined as the stages which a cell passes from one cell division to the next cell division.

Timing of cell cycle differs from species to species.

Usually from 8 to 20 hours.

Cell cycle has two phases:-

Mitotic Phase / M Phase

Interphase

Most of cells life is spent in the Interphase.

Cell is Metabolically active, synthesizing materials such as proteins, lipids and other biologically
important molecules and Growing during Interphase.

Page 210…

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Figure 10-5 The eukaryotic cell cycle

The cell cycle, a successive series of events in the life of a cell, includes interphase (G1, S, and G2)
and M phase (mitosis and cytokinesis). Proportionate amounts of time spent at each stage vary
among species, cell types, and growth conditions. If the cell cycle were a period of 12 hours, G1
would be about 5 hours, S would be 4.5 hours, G2 would be 2 hours, and M phase would be 30
minutes.

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Figure 10-6 Interphase and the stages of mitosis
(a) Cell carries out normal life activities. Chromosomes become duplicated.

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The interphase is divided in 3 sub phases.

G1 Phase / Gap Phase

Growth and normal metabolism.

Longest phase.
Cell that remain in this phase and do not divide in this stage is termed as in a Go stage.
At the end of G1 phase, enzymes required for DNA synthesis become more active.
At the end of the G1 phase proteins that will help to the cell to move to S phase will be synthesize.

S Phase / Synthesis Phase

DNA replication.
Histone proteins synthesized.

G2 Phase

Second gap phase.

Increased protein synthesis.
The final step in the cell’s preparation for mitosis.
G2 phase is usually the shortest compared to G1 and S phase.

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M Phase/ Mitotic Phase

Two phases which are :-

Mitosis which is a Nuclear Division that produces Two Nuclei
containing chromosomes which are genetically identical.

Cytokinesis which is division of the cytoplasm.

Mitosis consists of : Prophase Metaphase Anaphase and Telophase.

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 OVER VIEW OF MITOSIS

Figure 10-6 Interphase and the stages of mitosis

(d) Chromosomes line up along cell’s midplane. Spindle microtubules attach each chromosome to
both poles.

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 MITOTIC PHASE

PROPHASE P211…

Chromosome compaction.
Chromatin fibers starts to coil.
Duplicated chromosomes (sister chromatids) become visible under microscope.
The sister chromatids are attached to the Centromere.
A centromere is constricted region of the chromosome.

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Figure 10-7 Sister chromatids and centromeres
The sister chromatids, each consisting of tightly coiled chromatin fibers, are
tightly associated at their centromere regions, indicated by the brackets. Associated with each
centromere is a kinetochore, which serves as a microtubule attachment site. Kinetochores and
microtubules are not visible in this TeM of a metaphase chromosome.

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The two sister chromatid are held together by a protein complex call Cohesin.
Cohesin makes sure that the two sister chromatids separate during anaphase.

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 Figure 10-8 Cohesins

On the centromere there is a structure called Kinetochore.

Microtubules are attached on the kinetochore.

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Microtubule play an important role in chromosome separation during mitosis.
Microtubule originate from the poles of the dividing cell.
These microtubule form a structure called the Mitotic Spindle.
Two types of microtubules:-
Minus end near the poles.
Plus end at the equatorial plane of the cell

At the poles of the dividing cell there is a region called the Microtubule Organizing Center.
The microtubules originate from the MOC.
Animal cells have a pair of Centrioles in the center of the Microtubule organizing center.
The centrioles are surrounded by fibrils called the pericentriolar material.
The spindle microtubule ends in the pericentriolar fiber.
The microtubules do not touch the centrioles.
It is believed that the pericentriolar material is responsible for centriole duplication.
The centrioles are duplicated during the S Phase.
In late prophase, microtubules radiated form pericentriolar material and is called Asters.
The two asters migrate to the opposite ends of the nucleus forming the two poles of the mitotic
spindle.

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Figure 10-6 Prophase
(b) Long fibers of chromatin condense as compact mitotic chromosomes, each consisting of two
chromatids attached at their centromeres. Cytoskeleton is disassembled, and mitotic spindle forms
between centrioles, which have moved to poles of cell. Nuclear envelope begins to disassemble.

PROMETAPHASE

Nuclear membrane breaks down.

Nuclear membrane components are stored in vesicles to used again after mitosis.
Microtubules come into contact with chromosomes at the kinetochore.
Nucleolus shrinks and disappear.
Mitotic spindle is fully formed.

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The spindle microtubules shrink and grow as if to search and capture chromosomes at the
kinetochore.
Chromosome begin to move to mid plane/equatorial plate.

Prometaphase
(c) Spindle microtubules attach to kinetochores of chromosomes. Chromosomes begin to move
toward cell’s midplane.

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METAPHASE

All chromosomes at the cell mid plane/ metaphase plate/equatorial plate.

Both the chromatids are attached to the microtubules from opposite sides of the poles.
The mitotic spindle has 3 types of microtubules. Refer to diagram 10.9 Pg. 214
Polar microtubules/ non kinetochore microtubules
Kinetochore microtubules
Astral microtubule

Figure 10-9 Metaphase

One end of each microtubule of this animal cell is associated with one of the poles. Astral
microtubules (green) radiate in all directions, forming the aster.
Kinetochore microtubules (red) connect the kinetochores to the poles, and polar (nonkinetochore)
microtubules (blue) overlap at the midplane.

ANAPHASE

*Separation of sister chromatids*

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Cohesin proteins holding the sister chromatids together starts to breakdown.
Sister chromatids separate.
Now the chromatids are now known as Chromosome.
Chromosomes move to opposite poles.
The microtubules shorten from the kinetochore end. The microtubules are changed to tubulin
(depolymerize ) unit during shortening. Refer and Read Figure 10.10
The kinetochore is leading towards the poles.
Anaphase ends when all the chromosomes reach the poles.

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(e) Sister chromatids separate at their centromeres. One group of chromosomes moves toward each
pole of cell. Spindle poles move farther apart.

TELOPHASE P 215…

Chromosomes arrive at poles.

Chromosome DEcondense by uncoiling.
Nuclear membrane formed around each set of chromosome.
Spindle microtubules disappear.
Nucleolus appear.

TELOPHASE

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(f) Chromosomes are grouped at poles. Chromosomes decondense, and nuclear envelopes begin to
form. Cytokinesis produces two daughter cells.

CYTOKINESIS P 215

Division of cytoplasm to produce two daughter cells.

The last of the M phase.

Cytokinesis in animal or fungal cell :-

- Actomyosin contractile ring is formed and is attached to plasma membrane.

- Actomyosin contractile ring encircle the cell at right angle to the spindle.
- The contractile ring is made from actin and myosin filaments.
- It is the myosin filaments that contracts and causes the actin to constrict and divide the cell
into two daughter cells.
- It forms a cleavage furrow before dividing the cell into two daughter cells.
-

-
-
- Figure 10-11 Cytokinesis in animal cells
- (a) TEM of the equatorial region of a cultured animal cell undergoing cytokinesis. Note the
cleavage furrow. Dividing fungal cells also have a contractile ring that causes cytokinesis.
-

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Cytokinesis in plant cell :- Figure 10.11

- A Cell Plate is formed in the center of the cell.

- The cell plate grows towards the cell wall.
- Vesicle gather in the center of the cell. The vesicle is formed from the Golgi complex.
- Small vesicle fuse together forming large vesicle
- Finally one large vesicle is formed and the components of the cell wall is deposited to form
the cell wall.
- A transverse cell wall is synthesize between the two cells.

Figure 10-11 Cytokinesis in plant cells

(b) Cell plate formation during cytokinesis in a plant cell. The TEM shows a maple leaf cell (Acer
saccharinum) undergoing cytokinesis

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BINARY FISSION Figure 10.12

Prokaryotes reproduce asexually by binary fission.

The circular DNA replicates beginning at the Origin of Replication site.
Then it replicate from both sides until they meet to produce a daughter chromosome.
Cytokinesis to form two daughter cells is controlled by the Z ring.
Z ring is a ring of protein that circles the center of the cell.
The plasma membrane grows inwards between the two DNA dividing the cell cytoplasm in half.

Figure 10.12: Binary fission.

The bacterial chromosome is much longer than depicted here and is tethered to the plasma
membrane at one spot (not shown).
1 DNA replication begins at single site on bacterial chromosome.
2 Replication continues, as replication enzymes work in both directions from site where replication
began.
3 Replication is completed, and daughter chromosomes separate. Z ring forms at cell’s midsection.
Cell begins to divide, as plasma membrane grows inward. A new cell wall forms.

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4 Binary fission is complete. Two identical daughter cells result.

Figure 10-10 HOW MICROTUBULES SHORTEN.

Using laser photobleaching to determine how chromosomes are transported toward the spindle
poles during anaphase .

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REGULATION OF THE CELL CYCLE

CYCLIN

cDK = cyclin Dependent Protein Kinase

Page 217…..
In optimal condition prokaryotic cell divide every 20 minutes.
Eukaryotic cells takes longer time.
Skeletal muscles stop dividing [Go] after a few months of life.
Blood forming cells, digestive tract cell, skin divides throughout life.
Under optimal conditions of :- Nutrition, Temperature, pH the length of eukaryotic cell cycle is
constant for any cell type.
If the conditions are not favourable, the generation time/cell division slows down.

REGULATORY MOLECULES control the cell cycle.

These regulatory molecules are components found in the cell and they play an important part in the
CELL CYCLE CONTROL SYSTEM.

These Regulatory molecules trigger a specific sequence of events during the cell cycle..
Cell Cycle consists of hundreds of sequential events that move in an orderly manner.
If they are not carefully controlled then this can lead to disastrous consequences. Eg. Cancer.

CELL CYCLE CHECK POINT

Cell cycle check points make sure that all of the events in a specific stage ( G1, S, G2, Mitosis) have
been completed before the next stage can proceed.

Genetic information of the Cell cycle Checkpoint temporarily block key events from starting during
the cell cycle.
( For example : you need to pass your UPSR examination before taking the PMR examinations. And you need to pass your PMR
examinations before taking the SPM examinations.)

The checkpoints are inactivated once they have done their job. This is to allow the cell to proceed to
the next stage of the cell cycle.

Genes that codes for checkpoint molecules are important for the Cell Cycle to function normally.

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If the Check Point genes are defective, this might cause cancer or other serious disease.

Eg. If the Metaphase – Anaphase Checkpoint molecules become non functional.

Cell will move from Metaphase to Anaphase too early. This will result in daughter cells having too
few or too many chromosomes. Eg Down Syndrome or cancer.

Diagram of sister chromatids not separating.

Non Disjunction

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Figure 10-13 Key checkpoints in the cell cycle

The cell cycle consists of hundreds of sequential events. The red bars show three important
checkpoints that determine that previous steps are completed so that the next steps may proceed.
Each checkpoint is inactivated after it has performed its function, allowing the cell cycle to continue.

1. G1–S checkpoint: The first key checkpoint ensures that the cell has the necessary growth factors,
nutrients, and enzymes to synthesize DNA. Without the proper signals that the cell is ready to
proceed, the checkpoint will not let DNA synthesis begin.

2. G2–M checkpoint: This cell-cycle checkpoint ensures that DNA replication is finished before the
cell begins mitosis. If a cell has damaged or unreplicated DNA, the checkpoint will not let the cell
undergo mitosis.

3. Metaphase–anaphase checkpoint: Sometimes called the spindle checkpoint, this checkpoint

occurs at the end of metaphase and prevents anaphase from occurring until all kinetochores are
properly attached to spindle fibers along the cell’s midplane.

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G1 –S checkpoint

The first key check point ensures that the cell has the necessary:-

 Growth factors
 Nutrients
 Enzymes to Synthesize DNA.

Without the proper signals the cell will NOT move to the S Phase.

• Called “restriction point” in mammalian cells.

• Decides whether cell should divide, delay division, or enter resting phase (G0 phase) by
assessing progress/growth of cell.

G2- M checkpoint

This check point CHECKS that DNA REPLICATION has finished without any errors before the cell
divide in mitosis stage. If the cell is damaged or the DNA replication has gone wrong, this check point
will not allow the cell to proceed to M Phase.

• Determines whether cycle can proceed to M.

• Decides whether M stage can start, by assessing success of DNA replication at phase S.

• Entry to M phase can be blocked by

1. Incomplete DNA replication,

2. DNA damage, and

3. insufficient cell size.

METAPHASE – ANAPHASE checkpoint

The Spindle checkpoint. This check point occur at the end of Metaphase and stop Anaphase from
happening if the spindle fibers/microtubules are not properly attached to the Kinetochores of the
chromosomes.

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CHEMICAL REGULATION OF THE CELL CYCLE

The TWO key molecules regulating the cell cycle are :-

1- PROTEIN KINASE

These are ENZYMES that activate or inactivate other proteins by

Phosphorylating ( Add Phosphate Group) them.

An example of this protein kinase is CYCLIN DEPENDENT KINASES (Cdks).

The activity of various Cdk increase and decrease as the cell moves through the cell cycle.

Cdk can only work when they bind with CYCLIN.

2- CYCLIN

The concentration of Cyclin moves up and down during the cell cycle.

Cyclin is being synthesize and broken down during the cell cycle.
Cyclin level in cancer cells are often higher than normal cells.

ACTION OF CYCLIN-CDK COMPLEX

a. When a specific Cdk binds with Cyclin it forms a cyclin – Cdk complex.
b. Cyclin – Cdk Complex phosphorylate enzymes and other proteins.
c. Some of these proteins become activated when they are phosphorylated.
d. Some proteins are inactivated when they are phosphorylated.
e. Example :- The phosphorylation of protein p27. Protein p27 is a major inhibitor of cell division.
f. As various enzymes are activated or inactivated by phosphorylation the activity of the cell will
change.
g. When the level of p27 goes down in a non dividing cell, it will begin to divide.

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The levels of the different cyclins vary considerably across the cell cycle, as shown in the diagram at right. A
typical cyclin is present at low levels for most of the cycle, but increases strongly at the stage where it's needed.
M cyclin, for example, peaks dramatically at the transition from G2 to M phase. G1, cyclins are unusual in that
they are needed for much of the cell cycle.

TYPES OF CYCLIN-CDK COMPLEX IN EUKARYOTIC CELL

There are four types of Cyclin-Cdk Complex.

1. G1 – Cdk
2. G1/ S-Cdk
3. S- Cdk
4. M- Cdk

Each one of these Cdk cyclin complex phosphorylate a different group of protein.

G1- Cdk Prepares the cell to pass from G1 phase to S phase

G1/S - Cdk Commits the cell to undergo DNA Replication
S- Cdk STARTS DNA replication
M-Cdk Promotes the events of Mitosis.
Chromosome condensation.
The breakdown of nuclear envelope.
Mitotic spindle/microtubule formation.
M-Cdk also activates Anaphase-Promoting
Complex (APC) at the end of metaphase phase.
APC starts the Anaphase by breaking down
Cohesins that hold the sister chromatids together
allowing them to separate. Refer to Diagram 1a
below.
At this point Cyclin is broken down thus M- Cdk
activity drops. This will cause the mitotic spindle to
disassemble and the cell exits mitosis.

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Diagram 1a

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Figure 10-14 Molecular control of the cell cycle
This diagram is a simplified view of the control system that triggers the cell to move from G2 to M
phase.

1 Cyclin is synthesized and accumulates.

2 Cdk BINDS with cyclin, forming M-Cdk, a cyclin–Cdk complex.

3 M-Cdk phosphorylates proteins, activating those that facilitate mitosis

and inactivating those that inhibit mitosis

4 An activated enzyme complex recognizes a specific amino acid sequence in cyclin and targets it
for destruction. When cyclin is degraded, M-Cdk activity is terminated, and the cells formed by
mitosis enter G1.

5 Cdk is not degraded but is recycled and reused . CYCLIN IS BROKEN DOWN

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Cancer drugs can stop the cell cycle at specific checkpoints.

Some of this drugs :-

 Prevent DNA synthesis./DNA replication

 Inhibit the synthesis of protein that control the cell cycle.
 Inhibit the synthesis of structural proteins that makes mitotic spindle./stop microtubule
production

Thus slowing down cancerous cell division.

But these anti cancer drugs have side effects such as nausea and hair loss due to the drugs effect
on normal cells that divide rapidly in the digestive system and hair follicles.

MEIOSIS..skip first……end of lecture

In sexual reproduction the union of two haploid [n] gametes will produce a diploid [2n] zygote.
Sexual reproduction will produce genetic variation.
This will allow the offspring a better chance to adapt and survive better in the environment.
If a cell contain two set of chromosomes it is known as diploid [2n].
If it contains a single set of chromosome it is known as haploid [n].
An individual with more than two sets of chromosome is called polyploid.
If there is no meiosis, then the gametes will be 2n + 2n producing a 4n zygote.
Polyploidy or doubling the amount of chromosome sets will produce mutants and will not survive.
Each chromosome in a somatic animal or plant cell has a partner chromosome.
They are known as Homologous chromosome.

Homologous chromosome have the same :-

Size
Shape
Position of centromere

Homologous chromosomes can be considered almost identical to each other but may differ
genetically.
Humans have 46 chromosomes or 23 homologous pairs.

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A cell division that reduces the chromosome number is called meiosis.
It reduces the chromosome number to half.
From 2n to n. From diploid to haploid.
It undergo TWO cell division.
Produces FOUR haploid cells.
There is an exchange of genetic material. Meosis 1…Prophase 1

Basic differences between Mitosis and Meiosis p 220

1. Meiosis is made up of two nuclear division and two cytoplasmic division. It produce 4 haploid
daughter cells.
2. DNA replication occurs during the interphase of the first meiotic division.
3. Each of the 4 daughter cells have haploid chromosome number.
4. All the 4 daughter cells have unique combination of genes due to crossing over.

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Figure 10-15 Overview of meiosis

This figure begins with a diploid cell with four unduplicated chromosomes. The chromosomes derived from one parent are
shown in blue, and those from the other parent are red. Homologous pairs are similar in size and shape.

Meiosis is divided into two stages.

Meiosis I and Meiosis II.

Meiosis I is reduction division where homologous chromosomes separate.

During Meiosis I , homologous chromosome pair (synapsis), have crossing over and separate.
Meiosis I produces two haploid daughter cell.
SEPARATION OF HOMOLOGOUS CHROMOSOME.
RANDOM ASSORTMENT
CROSSING OVER
PROPHASE 1

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Meiosis II is basically mitosis , where sister chromatid divide.
Meiosis II produces 4 daughter cells.
SEPARATION OF SISTER CHROMATIDS
Refer to Figure 10.15

Figure 10-16 Interphase and the stages of meiosis

Interphase: Interphase preceding meiosis; DNA replicates. S PHASE

Prophase I: Homologous chromosomes synapse and exchange segments by crossing-over; nuclear

envelope breaks down.

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MEIOSIS 1

PROPHASE 1

Chromosome duplicate during S phase of Interphase.

The chromosome have two chromatids and held together by cohesin.
*Synapsis and Crossing Over

Homologous chromosomes come side by side. We call this synapsis.

Maternal and paternal chromosome undergo synapsis.
This structure now have 4 chromatids and now is called a Tetrad.
Homologous chromosomes are attached together by the synaptonemal complex.( Fig.10.17)
Synaptonemal complex helps crossing over.
Crossing over :- a process where homologous chromosome exchange their chromatids/genetic
material. Enzymes breaks and joins together DNA molecules.
Crossing over produces genetic variation by genetic recombination.

Figure 10-17 A synaptonemal complex

Synapsing homologous chromosomes in meiotic prophase I are held together by a synaptonemal

complex, composed mainly of protein.

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A spindle is formed during prophase I.
Microtubules forms.
In animal cells a pair of centrioles moves to opposite poles of the cell
Astral microtubules forms.

In late prophase the are held together at specific region called the Chiasma.
This is the crossing over site where homologous chromatid exchange genetic material.

Figure 10-18 A meiotic tetrad with two chiasmata The two chiasmata are the result of separate
crossing-over events.
.
A drawing showing the structure of the tetrad. The paternal chromatids are blue, and the maternal
chromatids are red.

METAPHASE I

Tetrad align at mid plane.

Microtubule attached to the kinetochore .

ANAPHASE I

Separation of homologous chromosome.

Each move to opposite poles.
Sister chromatid still attached at the centromere.

TELOPHASE I

Chromatids decondense.
Nuclear envelope reorganize.
Cytokinesis occur.
Interkinesis occur /a short pause. ….but its not a true Interphase.
No S phase, No DNA replication during Interkinesis.

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Figure 10-16 Interphase and the stages of meiosis

Interphase: Interphase preceding meiosis; DNA replicates.

Prophase I: Homologous chromosomes synapse and exchange segments by crossing-over; nuclear

envelope breaks down.

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Anaphase 1- Separation of Homologous chromosomes

Anaphase II – Separation of sister chromatids.

MEIOSIS II
 Similar to mitosis
 Separation of sister chromatids

PROPHASE II

At this stage chromosomes remain partially condensed.

This stage is very brief.
This stage is similar to mitotic prophase.
No Pairing of homologous chromosome.
No crossing over.

METAPHASE II

Chromosome line up at the mid plane of the cell.

Compare the difference between Meiosis I and Meiosis II

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ANAPHASE II

Separation of sister chromatid.

TELOPHASE II

Chromosomes move to the poles.

Nuclear envelope forms.
Chromosome uncoil to form chromatin.
Cytokinesis occurs.

Two causes of genetic variation during meiosis.

1. DNA segments are exchange between paternal and maternal homologous chromosomes.
Crossing over.
2. Independent assortment of chromosomes at Anaphase I. Paternal and Maternal
chromosomes separate independently. ..see animation by Mr mahathir

DIFFERRENCES BETWEEN MITOSIS AND MEIOSIS

Mitosis:-
1. Single nuclear division.
2. Separation of sister chromatids.
3. Two daughter cells formed.
4. A diploid cell will produce two diploid daughter cells.
5. A haploid cell will produce two haploid daughter cells.
6. Homologous chromosome do not associate physically. No synapsis.
7. No crossing over.

Meiosis:-

1. Diploid cells can undergo meiosis. Haploid cannot undergo

meiosis.
2. Undergo two nuclear division which is Meiosis I and Meiosis II.
3. In Prophase I homologous chromosome undergo synapsis to form
tetrad.
4. Reduction division. Homologous chromosomes separate during
Meiosis I. (Anaphase I)
5. Sister chromatids separate during Meiosis II. ( Anaphase II)
6. Four haploid daughter cells/gametes are formed.
7. The four gametes or daughter cells are genetically different.

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Cancer Cell and Cell Development.

• Cancer – the unrestrained/uncontrolled growth of cells  failure of cell cycle control.

• Caused by “Guardian Angel gene”, p53  plays important role in G1 checkpoint.

• Gene’s product is the protein, p53.

 Checks whether DNA has successfully replicated & is undamaged.

– If DNA is damaged, p53 halts/pause cell division and stimulate special enzymes (DNA
repair enzyme) to repair it.

– Once repaired, p53 allows cell division to proceed.

• Because p53 halts/pauses division of damaged cells, p53 is considered to be tumor

suppressor gene.

• If DNA can’t be repaired, p53 directs the cell to kill itself = apoptosis (cell suicide)  to
prevent development of many mutated cells.

• p53 is absent or damaged (nonfunctional/ defective) in cancerous cells  undergo repeated

cell division without being halted at G1 checkpoint.

• Cancer cells divide excessively and invade other tissues because they are free of body’s
control mechanisms.

– Cancer cells do not stop dividing when growth factors are depleted because they:

i. manufacture their own growth factors

ii. have abnormality in signaling pathway

iii. have abnormal cell cycle control system.

• If and when they stop dividing, they do so at random points, not at normal checkpoints in
cell cycle.

• May divide indefinitely if they have a continual supply of nutrients.

• May be “immortal.”

– Example: HeLa cells from a tumor removed from a woman (Henrietta Lacks) in 1951
are still reproducing in culture.

• Their abnormal behavior begins when a single normal cell in a tissue undergoes
transformation that converts it to a cancer cell.

– Normally, immune system recognizes and destroys transformed cells.

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 – However, cells that evade destruction proliferate to form tumor, a mass of abnormal
cells.

• If abnormal cells remain at originating site, lump is called a benign tumor.

– Most do not cause serious problems and can be fully removed by surgery.

• In malignant tumor, cells become invasive enough to impair functions of one or more
organs.

Abnormality of cells of malignant tumors:

1) Excessive proliferation/cell division.

2) Unusual chromosome number.

3) Metabolic abnormalities - may be disabled, and may cease to function in constructive way.

4) Often lose attachment to nearby cells & are carried by blood and lymph system to other
tissues, and start more tumors in an event called metastasis.

5) May secrete signal molecules that cause blood vessels to grow toward tumor.

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 • Carcinogens (cancer-causing agents) - cigarette smoke, ultraviolet radiation, X-ray, and more
than 1,000 known chemicals, including numerous pesticides, household products, and food
additives causes mutation of p53 genes.

• Proto-oncogenes: genes that normally promote cell division.

• Oncogenes: mutated form of proto-oncogenes that causes unrestrained cell growth and
division.

• Tumor-suppressor genes: Genes that normally inhibits cell division, but when mutated, fail
to keep a cancer from growing.

Treatments for metastasizing cancers:

i. High-energy radiation

ii. Chemotherapy with toxic drugs.

iii. These treatments target actively dividing cells.

iv. Chemotherapeutic drugs interfere with specific steps in cell cycle.

v. For example, Taxol prevents mitotic depolymerization, preventing cells from

proceeding past metaphase.

vi. Side effects of chemotherapy are due to drug’s effects on normal cells.

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CANCER AND CELL DEVELOPMENT

Cancer cells do not undergo biological inhibition.

Normal cells are tightly regulated by control mechanisms.
It allows them to divide when necessary and stop them from growing and dividing
inappropriately.
Cells in many tissues are prevented from dividing. They only divide when there is a need to
replace dead or damaged cells.
Cancer cell has escaped all of this control and divide continuously.
Cancer cell has abnormal growth pattern.

Cancer cells produce a mass of tissues called a TUMOR or NEOPLASM.

If cancer cells spreads to other part of the body, it is called Metastasis.
Metastatic cancer cells invade and divide in other tissues.
Lung cancer is deadly because the cancer cells can move through the blood vessels and
spread through out the body.
Cancer driver genes if altered or undergo mutation will cause uncontrolled cell to division.
Oncogenes is a cancer activating gene.

The normal products of the Proto oncogene are components of 12 signal transduction
pathways.

Which will control , regulate cell growth , cell division and cell development.

If proto oncogenes mutate, one the signalling products changes and short circuits the
pathways leading to uncontrolled cell growth hence cancer.

Cancer is caused by oncogenes together with loss of the expression of other cancer drivers
called Tumor Supressor Genes .

Cancer = Proto Oncogene Mutate jadi Oncogene + Mutated Tumor Supressor Gene.

CANCER = ONCOGENE + MUTATED TUMOR SUPRESSOR GENE

Oncogenes – Cancer accelerator

Tumor Supressor Genes – Stops abnormal cell growth and division.

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There are 125 driver genes:
- 54 are oncogenes
- 71 are tumor suppressor genes.

In breast cancer, pancreatic cancer, brain cancer and colorectal cancer = 3 to 6 driver genes
are mutated.

OCOGENES PRODUCE ALTERED COMPONENTS THAT PLAY A ROLE IN CELL SIGNALLING

PATHWAY WHICH CONTROL CELL

Figure 17-20 Oncogenes inappropriately activate signaling pathways that regulate cell growth and differentiation

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Many cancers arise from the activation of proto-oncogenes in signaling pathways that control cell growth and
differentiation. Mutations that cause the proto-oncogenes that code for the EGF receptor, Ras, or Raf to function as
oncogenes are found in many different types of cancer cells. An activating mutation in any of these three proto-
oncogenes that encode components of the MAP kinase pathway can result in the production of an oncoprotein (shown
in red) that would permanently switch the pathway “on,” continuously stimulating growth and cell division in a newly
formed cancer cell and its progeny.

When Proto- oncogenes mutate they become Oncogene.

Oncogene activate signalling pathway that trigger cell division.
The produce proteins in the pathway that causes the cell to divide continuously.
Like the ON SWITCH always on.

RAS Gene in Figure 17.20 undergo mutation to produce a slightly different RAS Protein.
A normal RAS protein acts as an ON /OFF switch.
But a mutated RAS gene produces a slightly different RAS protein which always gives the ON
signal on the pathway continuously and causes continuous cell division.

HELA LINE

https://www.youtube.com/watch?v=xHIooZqKesM

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