CELL CYCLE

NUR MAHMUDAH
nurmahmudah12@gmail.com
CELL (EUKARYOT)
CELL CYCLE
 Cells reproduce themselves.
 Somatic cell (soma= body) :any cell of the body.

 Germ cell (germ=gamete) : sperm or oocyte.

Cells must be able to proliferate

- during development
- wound healing
- stem cells in blood, small intestine, immune system
For cells to copy themselves they need to:

- Grow; make more stuff; e.g. proteins, lipids

- Copy their genetic material

- Segregate contents to daughter cells, especially…
- Segregate replicated chromosomes to daughter cells
 INTERPHASE:
G1 + S + G2

START
or
Restriction Point

Figure 8.3b The Biology of Cancer (© Garland Science 2007)

 Cell Cycle Commandments
A cell resting in quiescence (G0) must not reenter the
cycle unless a proper mitogenic signal is received.

A terminally differentiated cell must not reenter the

cycle.
A cell must not start to replicate DNA unless its mass is
sufficient to support cell division.

A cell must replicate every DNA sequence once, and only

once, during each cell division.

If the DNA is damaged, a cell must repair the damage before

cell division.

A cell must not divide until DNA replication has been

completed.
Each cell must receive a complete complement of replicated
DNA.
 The Restriction Point: Integrating GO : NO-GO Signals

Figure 8.6 The Biology of Cancer (© Garland Science 2007)

 The Restriction Point: Integrating GO : NO-GO Signals

Figure 8.1 The Biology of Cancer (© Garland Science 2007)

Loss of cell cycle control at the Restriction Poin
Two types of genes are mutated in cancer:
G0

proto-oncogenes
M Activity: stimulate cell cycle progression
Mutation in cancer: gain of function
G2 G1 proto-oncogene = wt; oncogene = mutant
Examples: cyclin D1, Mdm2, myc, ras

S
tumor suppressors
Activity: Inhibit cell cycle progression
Mutation in cancer: loss of function
Examples: Rb, p53, p16, ARF, PTEN
Cell Cycle Checkpoints
The Guardian Mechanisms of
the Genome

THEY ARE DISRUPTED

IN CANCER!

Figure 8.4 The Biology of Cancer (© Garland Science 2007)

 CELL CYCLE CHECKPOINTS
 If cell size inadequate

 G1 or G2 arrest
 If nutrient supply inadequate

 G1 arrest
 If an essential external stimulus is
lacking
 G1 arrest (at R)
 If the DNA is not replicated

 S arrest
 If DNA damage is detected

 G1 or G2 arrest
 If the spindle formation is improper,
chromosome misalignment R
 M-phase arrest
S Phase of the Cell Cycle

MCM
Helicase
 S Phase of the Cell Cycle

During the S phase, the

duplicated DNA is rearranged
through cohesion to form two
sister-chromatids attached to
each other by cohesins

The cohesins will be removed

during mitosis to allow sister-
chromatid separation
PHASES OF MITOSIS
G2 of Interphase

Prophase Prometaphase Metaphase

Anaphase Telophase & beginning Completion of cytokines

of cytokinesis
Mitosis
 PROPHASE
1. Nuclear chromatin starts to
become organized and condenses
into thick strands that eventually
become chromosomes observable
in the optical microscope.
2. The nucleoli, primarily responsible
for the production of ribosomal
RNA, begin to disappear as the
chromosomes condense.
3. The mitotic spindle, which is
assembled by the centrosomes
begins to appear along the
periphery of the nuclear
membrane. These are called asters
or stars
4. Centrosomes begin to move apart
MITOSIS
 Profase
 PROMETAPHASE
 Nuclear membrane begins to
fragment
 This allows spindle fibers to
invade the nuclear space and
interact with chromosomes
 Chromosomes are extremely
dense and each sister chromatid
has a protein complex at the
centromere called a kinetochore
 Some microtubules (spindle
fibers) attach to chromosome
kinetochores
 Other microtubules (spindle
fibers) interact with those from
the opposite pole of the mitotic
spindle
 METAPHASE

 Centrosomes are at opposite

poles
 The chromosomes, attached
to the kinetochore
microtubules, begin to align
in a single plane (known as
the metaphase plate)
midway between the spindle
poles
 Each sister chromatid’s
kinetochore is attached to a
spindle fiber coming from
opposite poles
METAFASE
ANAPHASE
• Sister chromatids pull apart
and are now considered
daughter chromosomes
• * Hypothesis - the motor
proteins in the kinetochore
move the chromosome along
the microtubule toward the
poles.
• Nonkinetochore
microtubules lengthen,
pushing the centrosomes
further apart.
• At the end of anaphase, each
group of chromosomes is
clustered at opposite poles.
ANAFASE
 TELOPHASE
 In animal cells, the cleavage
furrow begins to form due to
an actin ring
(microfilaments)
 In plant cells there is no
cleavage furrow – a cell plate
forms (discussed later)
 Nuclear membrane begins to
re-form
 The mitotic spindle begins to
disassemble
 Chromosomes begin to return
to chromatin state
 Nucleolus begins to reappear
TELOFASE
INTERPHASE
Centrioles will replicate
once the cell is ready to
 Nucleus contains divide again

chromatin
 Only one set of centrioles
(one centrosome)
 Fully formed nuclear
membrane
 Fully formed nucleolus
 Mitosis in Newt
Lung Cells

blue = DNA
green = microtubules

Figure 8.3a The Biology of Cancer (© Garland Science 2007)

At the end of the day:
You need to do metaphase correctly
This requires organizing microtubules….
The Metaphase to Anaphase Transition:
The key step during mitosis

Metaphase to anaphase transition in a plant cell

 INTERPHASE:
G1 + S + G2

START
or
Restriction Point

Figure 8.3b The Biology of Cancer (© Garland Science 2007)

CYCLICAL CHANGES IN DNA OF CELL
Cyclin Dependent Kinases Regulate the Cell Cycle
 CDKS AND CYCLINS
Cyclin-dependent kinases (Cdks) are enzymes that are present in the cell cytoplasm
at all times.

However, they are inactive unless they are bound by a specific partner-protein
called a cyclin to form a Cdk-cyclin complex

The amount of cyclins in the cell changes – because they get degraded

A Cdk-cyclin complex will push the cell cycle forward.

TYPES OF CYCLINS AND CDKS
 There are many types of cyclins, but the 4 main ones
are:
 Cyclin D (G1 cyclin)
 Cyclin E (S-phase cyclin)
 Cyclin A (S-phase and mitotic cyclin)
 Cyclin B (mitotic cyclin)

 These are the 3 main cdks

 Cdk4 (G1 Cdk)
 Cdk2 (S-phase Cdk)
 Cdk1 (mitotic Cdk)

 The complex of Cdk1 and cyclin B is called mitosis

promoting factor (MPF) a.k.a maturation promoting
factor
 RISE AND FALL OF CYCLINS
Cyclin Concentration

Mitosis
Phosphorylation of CDK Targets Changes Their Activi

Now performs
a cell cycle function
 SOMATIC CELL CYCLE

 A nuclear division (mitosis,mitos = thread) and a

cytoplasmic division (cytokinesis, cyto=cell &
kinesis=movement)
 Produce two identical cells (same number and kind of
chromosomes as the original cell).
 Replaces dead or injured cells and adds new ones during
tissue growth.
SOMATIC CELL CYCLE
INTERPHASE
 G1 (gaps) : replicates most of its organelles, and
cytosolic components. Centrosomes replicates
begin (8 -10 hours).
 S (synthesis) : replicates DNA (8 hours).

 G2 : cell growth continues, enzymes and other

proteins are synthesized in preparation for cell
division, and replication of centrosomes is
completed (4-8 hours).
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 CONTROL OF CELL DESTINY
Cyclins (cellular
proteins ), so
named because
their levels rise
and fall during
the cell cycle.
Enzymes called
Cyclin dependent
protein kinases
(Cdks)-transfer a
phosphate group
from ATP to a
protein to activate
the protein.
CYCLIN
CDK
CELLULAR DEATH
 Cellular death is also regulated, apoptosis.
 In apoptosis, a triggering agent from either
outside or inside the cell causes “cell-suicide”
genes to produce enzymes that damage the cell in
several ways, including disruption of its
cytoskeleton and nucleus cell
shrinksphagocytosis by phagocyte
 Apoptosis is a normal type of cell death; in
contrast necrosis is a pathological type of cell
death that results from tissue injury.
REPRODUCTIVE CELL CYCLE
 special two step division called meiosis (number
of chromosomes is reduced by half).
 Produces four gametes (the cells needed to form
the next generation of sexually reproducing
organisms).
 Each gamete contain 23 chromosomes, all with a
unique combination of mom's and dad's genes
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THANK YOU