Cell Cycle

And its
Control

Bi1113
Spring 2021
Mayurika Lahiri
 Flow of discussion
v Overview of the cell cycle
G1phase
S phase Interphase
G2 phase
Mitosis phase (prophase, metaphase, anaphase, telophase, cytokinesis)

Ø Meiosis

v Intra-cellular control of the cell cycle

Cyclin-dependent kinase & Cyclins

v Extra-cellular control of the cell cycle

a. Mitogens
b. Growth factors
c. Survival factors
 Flow of discussion
v Overview of the cell cycle
G1phase
S phase Interphase
G2 phase
Mitosis phase (prophase, metaphase, anaphase, telophase, cytokinesis)

Ø Meiosis

v Intra-cellular control of the cell cycle

Cyclin-dependent kinase & Cyclins

v Extra-cellular control of the cell cycle

a. Mitogens
b. Growth factors
c. Survival factors
The continuity of life - is based upon the reproduction
of cells, or cell division
 Cell Division

Unicellular organisms reproduce by cell division

100 µm

(a) Reproduction. An amoeba,

a single-celled eukaryote, is
dividing into two cells. Each
new cell will be an individual
organism.
 Cell Division
• Multicellular organisms use cell division:
– Development from a fertilized cell
– Growth
– Repair
200 µm 20 µm

(b) Growth and development. (c) Tissue renewal. These dividing

This micrograph shows a bone marrow cells (arrow) will
sand dollar embryo shortly give rise to new blood cells.
after the fertilized egg divided,
forming two cells.
Cell Division

Molecular Biology of the Cell

Early Drosophila embryo
 Importance of Cell Division

• An integral part of the cell cycle

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

receives an exact copy of the genetic material, DNA

 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.

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 Two duplicated chromosomes
chromosomes
 Structure of Chromosomes
• The centromere is a constricted region of the chromosome containing a
specific DNA sequence, to which is bound 2 discs of protein called
kinetochores.
• Kinetochores serve as points of attachment for microtubules that move
the chromosomes during cell division:

Metaphase chromosome

Centromere
region of
chromosome Kinetochore
Kinetochore
microtubules

Sister Chromatids
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Structure of Chromosomes
Diploid - A cell possessing two copies of each chromosome (human body
cells).
• Homologous chromosomes are made up of sister chromatids
joined at the centromere.

Haploid - A cell possessing a single copy of each chromosome (human

sex cells).
 The Cell Cycle
A cell reproduces itself by carrying out an orderly sequence
of events in which it duplicates its contents and then divides
in two. This cycle of duplication and division is known as the
CELL CYCLE
Major events of the cell cycle

Duplicate accurately the vast amount of

DNA in the chromosomes and then
segregate the copies precisely into two
genetically identical daughter cells.

Chromosome duplication occurs during

S phase (S for DNA synthesis).
[Requires 10-12 hours]

Cell division occurs during M phase (M

for mitosis).
M phase comprises two major events:
nuclear division or mitosis and
cytoplasmic division or cytokinesis.
 The Central Governor of Growth and Proliferation

Cell cycle clock: Molecular circuitry operating in the nucleus that

processes and integrates a variety of afferent signals originating from the
outside and inside the cell and decides whether or not the cell should enter
in to the active cell cycle or retreat into a non-proliferating state

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

 Eukaryotic cell cycle is divided into four phases
• Interphase
– G1 - primary growth
– S - genome replicated
– G2 - secondary growth
• M - mitosis
• C - cytokinesis

G0
 Interphase

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

DNA duplication
during interphase

Mitosis

Diploid Cell
 Significance of Mitosis
• Permits growth and repair.
• In plants it retains the ability to divide throughout the
life of the plant
• In mammals, mitosis is necessary:
– Fertilized egg becomes an embryo
– Embryo becomes a foetus
– Allows a cut to heal or a broken bone to mend
 Mitosis

During the S phase, the duplicated

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

Gradually, the cohesins will be

removed to allow sister-chromatid
separation
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
Mitosis phase: Prophase What does the cell looks like?

What is happening?

• The chromatin fibers become more

tightly coiled, condensing into discrete
chromosomes observable with a light
microscope.
• The nucleoli disappear.
• Each duplicated chromosome PROPHASE
appears as two identical sister Aster
Early mitotic
chromatids joined together. spindle Centromere
• The mitotic spindle begins to form.
It is composed of the centrosomes
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 Chromosome, consisting
of two sister chromatids
between them.
 What does the cell looks like?
Mitosis phase: Prometaphase
What is happening?

• Nuclear envelope fragments

• Chromosomes become more
condensed
• A kinetochore is formed at the
centromere, the point where the
PROMETAPHASE
sister chromatids are attached
Fragments
• Microtubules attach at the Kinetochore
of nuclear
Nonkinetochore
kinetochores envelope
microtubules

Kinetochore
microtubule
 What does the cell looks like?
Mitosis phase: Metaphase
What is happening?

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
Metaphase
the spindle’s two poles. The 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
 What does the cell looks like?
Mitosis phase: Anaphase
What is happening?

• Each centromere splits making

two chromatids free
• Each chromatid moves toward a
pole
• Cell begins to elongate, caused
METAPHASE ANAPHASE TELOPHASE
by microtubules not associated
with the kinetochore Metaphase
plate Cleavage
furrow

Nuclear
envelope
Spindle Centrosome at Daughter forming
one spindle pole chromosomes
 What does the cell looks like?
Mitosis phase: Telophase
What is happening?

• Formation of nuclear membrane

and nucleolus
• Short and thick chromosomes
begin to elongate to form long and
thin chromatin
METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS
• Formation of theMetaphase
cleavage furrow -
a shallow groove in the
platecell near Cleavage Nucleolus
furrow
the old metaphase plate forming

• Cytokinesis = division of the

cytoplasm

Nuclear
envelope
Spindle Centrosome at Daughter forming
one spindle pole chromosomes
 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) envelope Nonkinetochore
microtubules

Nucleolus Nuclear Plasma Chromosome, consisting Kinetochore

envelope membrane of two sister chromatids microtubule
 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
 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) Fragments Kinetochore
of nuclear
extends from each centrosome envelope
Nonkinetochore
microtubules

Kinetochore
microtubule
 Kinetochore orientation ensures proper
division of chromosomes
Aster
Centrosome
Sister
chromatids
Microtubules Chromosomes Metaphase
plate

Kineto-
chores

Centrosome 1 µm
Overlapping on
nonkinetochore Kinetochore
Some spindle microtubules attach to microtubules microtubules opposite
the kinetochores of chromosomes sides
and move the chromosomes to the
metaphase plate
0.5 µm
Kinetochore In budding yeast, only 1 kinetochore
associates with 1 microtubule, while in
humans, 15-20 microtubules are bound to
each kinetochore.
Microtubule
The first human kinetochore proteins
identified were CENP-A, CENP-B and
CENP-C [centromere protein]

Microtubule

Kinetochore
The spindle is a bipolar array of microtubules which pull sister chromatids apart in
anaphase. The minus ends of the spindle are towards the two spindle poles and the
plus ends radiate outward from the pole.
Interpolar microtubules: [+] ends of some microtubules interact with the [+] ends of
microtubules from the other pole.
Kinetochore microtubules: [+] ends of microtubules are attached to sister chromatid
pairs at kinetochores located at centromeres of each sister chromatid.
Astral microtubules: Microtubules that radiate out from the poles and contact the cell
cortex, helping to position the spindle in the cell.
 Mitosis in a plant cell
Nucleus Chromatin Chromosome
Nucleolus condensing

Prophase. Prometaphase. Metaphase. The Anaphase. The Telophase.

1 2 3 4
The chromatin We now see discrete spindle is complete, chromatids of each Daughter nuclei are
is condensing. chromosomes; each and the chromosomes, chromosome have forming. Meanwhile,
The nucleolus is consists of two attached to microtubules separated, and the cytokinesis has
beginning to identical sister at their kinetochores, daughter chromosomes started: The cell
disappear. chromatids. Later are all at the metaphase are moving to the ends plate, which will
Although not in prometaphase, the plate. of cell as their divide the cytoplasm
yet visible nuclear envelop will kinetochore in two, is growing
in the micrograph, fragment. microtubles shorten. toward the perimeter
the mitotic spindle is of the parent cell.
staring to from.
 Cytokinesis ends cell division
• Cleavage of cell into two halves
• In a typical cell, cytokinesis
accompanies mitosis, BUT early
Drosophila embryos and some
mammalian hepatocytes and heart
muscles, mitosis occurs without
cytokinesis and thereby acquire
multiple nuclei (syncytium).
– Animal cells
§ Constriction belt of actin

and myosin II filaments

– Plant cells
§ Cell plate

– Fungi and protists

§ Constriction belt of actin

and myosin II filaments

 Cytokinesis In Animal And Plant Cells

100 µm
Cleavage furrow Vesicles Wall of 1 µm
forming parent 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)
Snapshots of Cell Division
Plant cell division Animal cell division
MITOSIS
 Meiosis

• Formation of Gametes (Eggs & Sperm)

• Called Reduction division
• Preceded by interphase which includes
chromosome replication
• Two meiotic divisions
• Meiosis I and Meiosis II
• Original cell is diploid (2n)
• Four daughter cells produced that are haploid (n)
 Significance of Meiosis

Two haploid (1n) gametes are brought together

through fertilization to form a diploid (2n) zygote
 SIGNIFICANCE OF MEIOSIS
Significance of Meiosis
• Meiosis must reduce the chromosome number by half
• Meiosis must reduce the chromosome number by half
• Fertilization then restores the 2n number
• Fertilization then restores the 2n number

from mom from dad child

Too
much!
meiosis reduces
genetic content

The
right
fatimaArivera number!
 Prokaryote Cell Division - Binary Fission
• Replication begins at a specific site called the origin of replication and
proceeds bidirectionally in a circle
• Cell elongates and the newly replicated DNA molecules are actively
partitioned.
• The cytoplasm is divided by growth of a new membrane and septum.
• Produces 2 daughter cells which are genetically identical (unless a
mutation occurred) to each other and to the original cell.

Origin of replication
Replication
Prokaryotic of DNA
genome

Elongation of cell and

partitioning of DNA

Formation of new membrane

and septum

Inward growth of septum

Cell pinches in two

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.