LS1001: BIOLOGY

Cell Cycle and Division

The cell cycle is a repeated pattern of growth

and division that occurs in eukaryotic cells.
This cycle consists of four phases: G1, S, G2 and
M
Dr. Samir K. Patra
Professor
Department of Life Science
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07 September 2019
 Functions of Cell Division

100 µm 200 µm 20 µm

(a) Reproduction. An amoeba,
a single-celled eukaryote, is
dividing into two cells. Each
new cell will be an individual
organism (LM).
(b) Growth and development. (c) Tissue renewal. These dividing
This micrograph shows a bone marrow cells (arrow) will
sand dollar embryo shortly after give rise to new blood cells (LM).
the fertilized egg divided, forming
two cells (LM).

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There are several factors that regulate the cell
cycle and assure a cell divides correctly.

1.Before a cell divides,

the DNA is checked
to make sure it has
replicated correctly. (If
DNA does not copy
itself correctly, a gene
mutation occurs.

DNA replication animation:click on

DNA picture
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2. Chemical Signals tell a cell when to start
and stop dividing.

(Target cells animation: click on go

sign)

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Neighboring cells communicate with dividing
cells to regulate their growth also.

(Normal contact inhibition

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 Cell Division

• An integral part of the cell cycle

• Results in genetically identical daughter cells
• Cells duplicate their genetic material
– Before they divide, ensuring that each daughter

cell receives an exact copy of the genetic

material, DNA

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 DNA
• Genetic information - genome
• Packaged into chromosomes

Figure 12.3
50 µm

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 Prokaryotic Chromosome
 The DNA of
prokaryotes
(bacteria) is one,
circular
chromosome
attached to the
inside of the cell
membrane

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 Eukaryotic Chromosomes
 All eukaryotic cells store genetic information
in chromosomes
 Most eukaryotes have between 10 and 50
chromosomes in their body cells
 Human body cells have 46 chromosomes or 23
identical pairs

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 Eukaryotic Chromosomes

 Each chromosome is composed of a single,

tightly coiled DNA molecule
 Chromosomes can’t be seen when cells
aren’t dividing and are called chromatin

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 Chromosomes in Dividing Cells

 Duplicated
chromosomes are
called chromatids
& are held
together by the
centromere

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Called Sister Chromatids 11
 Karyotype
 A picture of the
chromosomes from a
human cell arranged in
pairs by size

 First 22 pairs are called

autosomes

 Last pair are the sex

chromosomes

 XX female or XY male
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 Cell Reproduction
 Asexual reproduction involves a single cell
dividing to make 2 new, identical daughter
cells
 Mitosis & binary fission are examples of
asexual reproduction
 Sexual reproduction involves two cells
(egg & sperm) joining to make a new cell
(zygote) that is NOT identical to the
original cells
 Meiosis is an example
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 Chromosome Duplication
• In preparation for cell division, DNA is replicated and the chromosomes condense

• Each duplicated chromosome has two sister chromatids, which separate during
cell division

0.5 µm
A eukaryotic cell has multiple
chromosomes, one of which is
represented here. Before
duplication, each chromosome
has a single DNA molecule. Chromosome
duplication
(including DNA
synthesis)
Once duplicated, a chromosome
Centromere
consists of two sister chromatids
connected at the centromere. Each
chromatid contains a copy of the
DNA molecule.

Sister
Separation chromatids
of sister
chromatids
Mechanical processes separate
the sister chromatids into two
chromosomes and distribute
them to two daughter cells.
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Centrometers Sister chromatids
 Chromosome Duplication
• Because of duplication, each condensed chromosome
consists of 2 identical chromatids joined by a centromere.
• Each duplicated chromosome contains 2 identical DNA
molecules (unless a mutation occurred), one in each
chromatid:

Non-sister
chromatids

Centromere Duplication

Sister Sister
chromatids chromatids
Two unduplicated
chromosomes Two duplicated chromosomes
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Phases of the Cell Cycle
• Interphase
– G1 - primary growth
– S - genome replicated
– G2 - secondary growth
• M - mitosis
• C - cytokinesis

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Cell Cycle

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• The main stages of the cell cycle are gap 1,
synthesis, gap 2, and mitosis.

– Gap 1 (G1): cell growth and

normal functions
– DNA synthesis (S): copies
DNA
– Gap 2 (G2): additional growth
(chromatids become replicated
chromosomes)
– Mitosis (M): includes division
of the cell nucleus (mitosis)
and division of the cell
cytoplasm (cytokinesis)
• Mitosis occurs only if the cell is large enough and the DNA
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undamaged.
 Interphase
• Cells spend the majority of their cell cycle in interphase.
• The purpose of interphase is for cell growth.
• By the end of interphase a cell has two full sets of DNA (chromosomes) and
is large enough to begin the division process.

• G1 - Cells undergo majority of growth

• S - Each chromosome replicates (Synthesizes) to produce sister
chromatids
– Attached at centromere
– Contains attachment site (kinetochore)
• G2 - Chromosomes condense - Assemble machinery for division such
as centrioles

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 Mitosis
 Some haploid & diploid cells divide by mitosis.
 Each new cell receives one copy of every
chromosome that was present in the original cell.
 Produces 2 new cells that are both genetically
identical to the original cell.

DNA duplication
during interphase

Mitosis

Diploid Cell

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 Mitotic Division of an Animal Cell

G2 OF INTERPHASE PROPHASE PROMETAPHASE

Centrosomes Aster Fragments
(with centriole pairs) Chromatin Early mitotic Kinetochore
spindle Centromere of nuclear
(duplicated) Nonkinetochore
envelope
microtubules

Nucleolus Nuclear Plasma Chromosome, consisting Kinetochore

envelope membrane of two sister chromatids microtubule
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 Mitotic Division of an Animal Cell

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Metaphase
plate Cleavage Nucleolus
furrow forming

Nuclear
envelope
Spindle Centrosome at Daughter forming
one spindle pole chromosomes
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G2 of Interphase
• A nuclear envelope bounds
the nucleus.
• The nucleus contains one or
more nucleoli (singular,
nucleolus).
• Two centrosomes have
formed by replication of a
single centrosome.
• In animal cells, each G2 OF INTERPHASE
centrosome features two
Centrosomes
centrioles. (with centriole pairs) Chromatin
• Chromosomes, duplicated (duplicated)
during S phase, cannot be
seen individually because
they have not yet condensed.

The light micrographs show dividing lung cells

from a newt, which has 22 chromosomes in its
somatic cells (chromosomes appear blue,
microtubules green, intermediate filaments
red). For simplicity, the drawings show only
four chromosomes.
Nucleolus Nuclear Plasma
envelope membrane

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Prophase
• The chromatin fibers become
more tightly coiled, condensing
into discrete chromosomes
observable with a light
microscope.
• The nucleoli disappear.
• Each duplicated chromosome
appears as two identical sister
PROPHASE
chromatids joined together.
• The mitotic spindle begins to form. Early mitotic
Aster
It is composed of the centrosomes spindle Centromere
and the microtubules that extend
from them. The radial arrays of
shorter microtubules that extend
from the centrosomes are called
asters (“stars”).
• The centrosomes move away from
each other, apparently propelled
by the lengthening microtubules
between them.
Chromosome, consisting
of two sister chromatids
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Metaphase
• Metaphase is the longest stage of
mitosis, lasting about 20 minutes.
• The centrosomes are now at
opposite ends of the cell.
•The chromosomes convene on the
metaphase plate, an imaginary
METAPHASE
plane that is equidistant between
the spindle’s two poles. The Metaphase
plate
chromosomes’ centromeres lie on
the metaphase plate.
• For each chromosome, the
kinetochores of the sister
chromatids are attached to
kinetochore microtubules coming
from opposite poles.
• The entire apparatus of
microtubules is called the spindle
Spindle Centrosome at
because of its shape. one spindle pole

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 The Mitotic Spindle
• The spindle includes the centrosomes, the spindle
microtubules, and the asters
• The apparatus of microtubules controls
chromosome movement during mitosis
• The centrosome replicates, forming two
centrosomes that migrate to opposite ends of the
cell
• Assembly of spindle microtubules begins in the
centrosome, the microtubule organizing center
• An aster (a radial array of short microtubules)
extends from each centrosome

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 The Mitotic Spindle
• Some spindle microtubules attach to the kinetochores of
chromosomes and move the chromosomes to the
metaphase plate
• In anaphase, sister chromatids separate and move along
the kinetochore microtubules toward opposite ends of the
cell

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Anaphase
• Anaphase is the shortest stage of
mitosis, lasting only a few minutes.
• Anaphase begins when the two sister
chromatids of each pair suddenly part.
Each chromatid thus becomes a full-
fledged chromosome.
• The two liberated chromosomes begin
moving toward opposite ends of the cell, ANAPHASE
as their kinetochore microtubules
shorten. Because these microtubules are
attached at the centromere region, the
chromosomes move centromere first (at
about 1 µm/min).
• The cell elongates as the
nonkinetochore microtubules lengthen.
• By the end of anaphase, the two ends of
the cell have equivalent—and
complete—collections of chromosomes.
Daughter
chromosomes

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Telophase
• Two daughter nuclei begin to
form in the cell.
• Nuclear envelopes arise from
the fragments of the parent
cell’s nuclear envelope and TELOPHASE AND CYTOKINESIS
other portions of the
endomembrane system. Cleavage Nucleolus
furrow
• The chromosomes become forming

less condensed.
• Mitosis, the division of one
nucleus into two genetically
identical nuclei, is now
Nuclear
complete. envelope
forming

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 Mitosis in a plant cell
Nucleus Chromatine Chromosome
Nucleolus condensing

Metaphase. The
1 Prophase. 2 Prometaphase. 3 4 Anaphase. The 5 Telophase. Daughter
spindle is complete,
The chromatin We now see discrete chromatids of each nuclei are forming.
and the chromosomes,
is condensing. chromosomes; each chromosome have Meanwhile, cytokinesis
attached to microtubules
The nucleolus is consists of two separated, and the has started: The cell
at their kinetochores,
beginning to identical sister daughter chromosomes plate, which will
are all at the metaphase
disappear. chromatids. Later are moving to the ends divided the cytoplasm
plate.
Although not in prometaphase, the of cell as their in two, is growing
yet visible nuclear envelop will kinetochore toward the perimeter
in the micrograph, fragment. microtubles shorten. of the parent cell.
the mitotic spindle is
staring to from.

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Cytokinesis

•Cytokinesis is the division of the

cytoplasm into two individual cells.

•The process of cytokinesis differs

somewhat in plant and animal
cells.

•In animal cells, the cell membrane

forms a cleavage furrow that
eventually pinches the cell into two
nearly equal parts, each part
containing its own nucleus and
cytoplasmic organelles. 31
 Cytokinesis In Animal And Plant Cells

100 µm
Cleavage furrow Vesicles Wall of 1 µm
forming patent cell Cell plate
cell plate New cell wall

Contractile ring of Daughter cells

microfilaments
Daughter cells
(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM)
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 Cells divide at different rates
• The rate of cell division varies with the need
for those types of cells.

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 Uncontrolled Mitosis

 If mitosis is not
controlled, unlimited
cell division occurs
causing cancerous
tumors

 Oncogenes are special

proteins that increase
the chance that a
normal cell develops
into a tumor cell
Cancer cells 34
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 Differences
Normal Cell Division Cancer Cells

1. DNA is replicated 1. Mutations occur in the

properly. DNA when it is replicated.

2. Chemical signals start and 2. Chemical signals that start

stop the cell cycle. and stop the cell cycle are
ignored.
3. Cells communicate with 3. Cells do not communicate
each other so they don’t with each other and
become overcrowded. tumors form.

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 CELL CYCLE CHECKPOINTS
• A checkpoint in the cell cycle is a critical
control point where stop and go signals regulate
the cycle. 3 major checkpoints are found in the
G1, G2, and M phases. ... Controlled by G1
Cdks-cyclin.

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 CONTROL OF THE CELL CYCLE

If it wasn't controlled, your cells would continue to grow

and divide...over and over again!

A number of proteins regulate and control the cell cycle.

Tell the cell when is the proper time to grow and divide,

Stop the cell when the time's not right.

Clinically, cancer can be described as uncontrolled cell growth
and proliferation

Understanding cell cycle control has many implications for

cancer, especially for the development of therapeutics.

http://cancerquest.org/index.cfm?page=2463#
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If it wasn't controlled, your cells would continue to grow
and divide...over and over again!

A number of proteins regulate and control the cell cycle.

Tell the cell when is the proper time to grow and divide,

Stop the cell when the time's not right.

Clinically, cancer can be described as uncontrolled cell growth
and proliferation

Understanding cell cycle control has many implications for

cancer, especially for the development of therapeutics.

Control of the cell cycle 39

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 CONTROL OF THE CELL CYCLE
Three checkpoints:
The G1/S cell cycle checkpoint
G2/M DNA damage checkpoint
Mitosis checkpoint

Animation

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 G1/S cell cycle checkpoint

controls the passage of eukaryotic cells from the first 'gap'

phase (G1) into the DNA synthesis phase (S).

Checks:
That the size is CORRECT
That the environment is CORRECT
External agents regulate progression

Kinases – add a phosphate group (phosphorylate) 42

 G1/S cell cycle checkpoint
How do they do that?

Major proteins involved:

Cyclins (proteins) - level fluctuate in the cell cycle.
&
Cyclin dependent KINASES* (Cdks)
They add phosphate groups to proteins that control processes in
the cell cycle.
They only do this when the cyclins are present.

*Kinases – add a phosphate group (phosphorylate)

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FLICKING THE SWITCH ON

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 External Controls?

Many different stimuli exert G1 checkpoint control including

DNA damage, contact inhibition and growth factor withdrawal.

They act to inhibit kinases (in a mechanism similar to Jacob

Monod).

Growth factors, promoting cell division, stimulate transcription

of Cyclins

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• A key characteristic of stem cells is that they can divide for long periods of time
in an environment where most other cells are quiescent, prompting the question
of how they overcome the G1/S checkpoint of the cell cycle. Hatfield et al. used
fruit fly germline stem cells carrying a mutation in dicer-1, a gene essential for
miRNA biogenesis, to show that miRNAs are required for stem cells to bypass
the G1/S checkpoint. This suggests that miRNAs may be involved in the
mechanism that makes stem cells insensitive to environmental stimuli that
would normally halt most cells at the G1/S checkpoint. The implication is that
the mechanism used by stem cells to overcome this checkpoint could possibly
be usurped by tumor cells.

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 G2/M DNA damage checkpoint

The G2/M DNA damage checkpoint prevents the cell

from entering mitosis (M phase) if the genome is damaged.
It also checks if the cell is big enough (i.e. has the resources to
undergo mitosis)
Almost exclusively, internally controlled

Kinases – add a phosphate group (phosphorylate) 49

 M checkpoint

The M checkpoint is where the attachment of the spindle

fibres to the centromeres is assessed.
Only if this is correct can mitosis proceed.
Failure to attach spindle fibres correctly would lead to failure to
separate chromosomes

Kinases – add a phosphate group (phosphorylate) 50

 MITOSIS PROMOTING FACTOR

Fusion of mitotic cell with cells in other stages of the cell-cycle

causes chromosomes of the other cell to condense and the nucleus
to breakdown.
Mitotic cells must contain a mitosis -promoting factor (MPF) –
produced at the end of G2?
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MPF may:
• phosphorylate histone protein H1 to condense chromatin.
• phosphorylate nuclear lamins to break nuclear envelope.
•phosphorylate MAPs (microtubule-associated proteins)
resulting in the formation of spindle

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 Summary of Controls:

• Three checkpoints,
– G1 – assesses cell size, environment (contact inhibition)
– G2 – assesses success of DNA replication
– M – assesses have spindle fibres attached correctly to
the chromosomes
• Mitosis promoting factor - a protein (or number of
proteins) which causes chromosomes to
condense, nuclear membrane to disappear and so
cells to enter mitosis
• http://science.education.nih.gov/supplements/nih1/cancer/activities/activity2_animations.htm
• http://nobelprize.org/educational_games/medicine/2001/index.htmll

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http://cancerquest.org/index.cfm?page=193#

http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/main.html

http://nobelprize.org/medicine/educational/2001/index.html

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 Why Do we Need Meiosis?
 It is the fundamental basis of sexual
reproduction

 Two haploid (1n) gametes are brought

together through fertilization to
form a diploid (2n) zygote

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