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LS1001

Cell Cycle and Division

Dr Bibekanand Mallick
Associate Professor
Department of Life Science
NIT Rourkela
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The cell cycle is a repeated pattern of growth and
division that occurs in eukaryotic cells.
 A cell divide through generations to create a population of
cells called clone
 A cell that is about to divide is called mother cell and
product of division is called Daughter cells

Prokaryotes - Binary fission


Eukaryotes – Mitosis and Meiosis

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Functions of Cell Division
100 µm 200 µm 20 µm

(a) Reproduction. An amoeba, (c) Tissue renewal. These dividing


(b) Growth and development.
a single-celled eukaryote, is bone marrow cells (arrow) will
embryo shortly after
dividing into two cells. Each give rise to new blood cells.
the fertilized egg divided, forming
new cell will be an individual
two cells.
organism.

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Prokaryotic reproduction - Binary fission

 Asexual reproduction and cell division used by all prokaryotes (bacteria and
archaebacteria), and some organelles within eukaryotic organisms (e.g.,
mitochondria)

 This process results in the reproduction of a living prokaryotic cell (or


organelle) by division into two parts that each have the potential to grow to
the size of the original cell (or organelle)

 The single DNA molecule first replicates, then each copy attaches to a
different part of the cell membrane

 When the cell begins to pull apart, the replicated and original DNA
molecules are separated

 The consequence of this asexual method of reproduction is that all the cells
are genetically identical, meaning that they have the same genetic material

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Prokaryotic reproduction - Binary fission

• Bacteria reproduce
by binary fission
– 12  2  2 
2 3

24 2n (n=Number
of generation)
– Each succeeding generation,
assuming no cell death, doubles
the population
• Exponential growth rate
• Total population after certain time
Nt= N0 x 2n

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Prokaryotic reproduction - Binary fission
• E. coli has a generation time of 20 minutes. If you start with
1 E. coli cell, how many do you have after 2 hours?
• Nt = N0 X 2n
• Nt =1 x 26 = 64

• If it is 2 hours, then 6 generations


• 120 minutes/20 minutes = 6

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Eukaryotic cell division
Phases:
• Interphase – Growth of cells (between two M phase):
(G1 phase, S phase, G2 phase)
• Mitotic phase – Division occurs

 Cells spent most of the time in the


interphase before it starts dividing.

 For example, in a typical human


cell, interphase occupy 23 hours of
a 24-hour cycle, with 1 hour for M
phase.

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Cell cycle – G1 phase
 Cells accumulate energy and prepares themselves for next
phase

 Active synthesis of RNA and protein takes place that are


required for DNA synthesis

 Features – unreplicated DNA is present


Cell increase in size
Chromosome remain uncondensed

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Cell cycle – S phase
• Duplication of DNA, copy number of DNA is doubled
• Duplication of centrioles (produce spindle fibres)
• Loose bundle of chromatin
• Sister chromatids (identical pairs of DNA molecules) are
joined by centromere

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Cell Cycle – G2 Phase

• Preparation of cells to undergo cell division

• Formation of macromolecules required for spindle formation

• So, RNA and protein are actively produced, and organelles


are also multiplied

The centrosome is located in


the cytoplasm usually close to
the nucleus. It consists of
two centrioles

Aster?
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Cell Cycle – M Phase

• Where the division of cell occurs through mitosis or meiosis


phase

• Mitosis: The process that distributes duplicated


chromosomes exactly and equally to the daughter cells
followed by cytokinesis (The process that physically
separates two daughter cells from each other):

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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 Prophase


Metaphase
Anaphase
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Telophase
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
chromatids joined together. PROPHASE
• 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 Chromosome, consisting
between them. of two sister chromatids

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Metaphase

• Metaphase is the longest stage of


mitosis, lasting about 20 minutes. METAPHASE
• The centrosomes are now at Metaphase
opposite ends of the cell. plate

•The chromosomes convene on the


metaphase plate, an imaginary
plane that is equidistant between
the spindle’s two poles. The
chromosomes’ centromeres lie on
the metaphase plate.
•The entire apparatus of
microtubules is called the spindle
because of its shape. Spindle Centrosome at
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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Anaphase
• Anaphase is the shortest stage of

• Anaphase begins when the two sister


chromatids of each pair suddenly part. ANAPHASE
Each chromatid thus becomes a full-
fledged chromosome.

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

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Cytokinesis

•Cytokinesis is the division of the


cytoplasm into two individual 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.

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Uncontrolled Mitosis

 If mitosis is not controlled,


unlimited cell division
occurs causing cancerous
tumors

Cancer cells 20
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Cancer
When good cells go bad
• Cancer is one of the most common diseases in the
developed world:
• 1 in 4 deaths are due to cancer
• 1 in 17 deaths are due to lung cancer
• Lung cancer is the most common cancer in men
• Breast cancer is the most common cancer in women
• There are over 100 different forms of cancer
What is cancer?

• Caner is defined as the continuous uncontrolled


growth of cells.
• A tumor is any abnormal proliferation of cells.
• Benign tumors stays confined to its original location
• Malignant tumors are capable of invading
surrounding tissue or invading the entire body
• Tumors are classified as to their cell type
• Tumors can arise from any cell type in the body
Three cancer types

• Carcinomas; constitute 90% of cancers, are cancers


of epithelial cells
• Sarcomas; are rare and consist of tumors of
connective tissues (connective tissue, muscle, bone
etc.)
• Leukemias and lymphomas; constitute 8% of tumors.
Sometimes referred to as liquid tumors. Leukemias
arise from blood forming cells and lymphomas arise
from cells of the immune system (T and B cells).
Properties of cancer cells

Normal cells show Cancer cells lack


contact inhibition contact inhibition
Properties of cancer cells
They keep growing

And growing

And growing

And growing
1. Cancer and the cell cycle
checkpoints,
oncogenes
tumor suppressor genes

2. 6 Traits of cancerous cells

3. Origins of cancerous cells


DNA
Mitotic Phase (M)
DNA

DNA DNA
Interphase
DNA
DNA

G1
G2 Cell growth
Cell growth
preparation for
division
Interphase

S
DNA replication

DNA
DNA
DNA

Interphase
Proteins within the cell control the cell cycle

– Signals affecting critical checkpoints determine


whether the cell will divide (cyclins, kinases)

G1 checkpoint

Control
system

M checkpoint G2 checkpoint
Anchorage, cell density, and chemical growth
factors affect cell division

• In laboratory cultures, normal cells divide only


when attached to a surface
= anchorage dependent
• Cells continue dividing until they touch one
another
= density-dependent inhibition

Cells anchor to dish surface and


divide.

When cells have formed a


complete single layer, they stop
dividing (density-dependent
inhibition).

If some cells are scraped away,


the remaining cells divide to fill
the dish with a single layer and
then stop (density-dependent
inhibition).
• Growth factors are proteins secreted by cells
that stimulate other cells to divide

After forming a single layer, cells


have stopped dividing.

Providing an additional supply of


growth factors stimulates further
cell division.
• Growth factors bind to specific receptors on
the plasma membrane to trigger cell division

Growth factor

Plasma membrane

Relay
Receptor proteins G1 checkpoint
protein
Signal
transduction Cell cycle
pathway control
system
Traits of cancer cells

• 1. Independent of GROW signal from other


cells often, oncogenes. Ex. ras
• 2. Ignores STOP signal
defective damage control, so problems not
corrected.
Often, tumor suppressor genes. Ex. p53
Traits of cancer cells, continued

• 3. No cell suicide (apoptosis)


If this occurs, treatments which damage
dividing cells may not work.
• 4. No limit to cell divisions
telomeres rebuilt on ends of xsomes
new treatment target: telomerase
Traits of cancer cells, continued

• 5. Angiogenesis - formation of blood vessels

• 6. Metastasis - ability to move to other tissues


benign: do not move from tumor site
malignant: invasive cells, can travel in
blood and lymph system
• Malignant tumors can invade other tissues and
may kill the organism

Lymph
vessels

Tumor

Glandular
tissue

Metastasis

1 A tumor grows 2 Cancer cells invade 3 Cancer cells spread


from a single neighboring tissue. through lymph and
cancer cell. blood vessels to other
parts of the body.
How do normal cells become cancerous?
Differences

Normal Cell Cancer Cells

1. DNA is replicated 1. Mutations occur in the


properly. DNA when it is
replicated.
2. Chemical signals start and
stop the cell cycle. 2. Chemical signals that start
and stop the cell cycle are
3. Cells communicate with ignored.
each other so they don’t 3. Cells do not communicate
become overcrowded. with each other and
tumors form.
What causes cancer?

• Cancer arises from the mutation of a normal gene.


• Mutated genes that cause cancer are called oncogenes.
• It is thought that several mutations need to occur to give rise
to cancer
• Cells that are old or not functioning properly normally self
destruct and are replaced by new cells.
• However, cancerous cells do not self destruct and continue
to divide rapidly producing millions of new cancerous cells.
• A factor which brings about a mutation is called
a mutagen.

• A mutagen is mutagenic.

• Any agent that causes cancer is called a


carcinogen and is described as carcinogenic.

• So, some mutagens are carcinogenic.


Carcinogens
• Ionising radiation – X Rays, UV light

• Chemicals – tar from cigarettes

• Virus infection – papilloma virus can be responsible for


cervical cancer.

• Hereditary predisposition – Some families are more


susceptible to getting certain cancers. Remember you
can’t inherit cancer, its just that you are maybe more
susceptible to getting it.
Benign or malignant?
• Benign tumours do not spread from their site of origin but can
crowd out surrounding cells. Eg. brain tumour, warts.

• Malignant tumours can spread from the original site and cause
secondary tumours. This is called metastasis. They interfere
with neighbouring cells and can block blood vessels, the gut,
glands, lungs etc.

• Why are secondary tumours so bad?

• Both types of tumour can tire the body out as they both need a
huge amount of nutrients to sustain the rapid growth and
division of the cells.
What is a biopsy?
How is the biopsy analyzed?

Pathology

Proteomic profile

Patient’s
tissue sample or
blood sample Genomic profile
What does a pathologist look for
examining biopsy tissue?
What does a pathologist look for when he/she
examines biopsy tissue with a microscope?

Normal Hyperplasia Mild Carcinoma in


dysplasia situ (severe
dysplasia) Cancer
Hyperplasia refers to tissue (invasive)
Dysplasia is an abnormal type of
growth based on an excessive excessive cell proliferation
rate of cell division, leading to characterized by loss of normal
a larger than usual number of tissue arrangement and cell
cells. structure.
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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Meiosis
• The form of cell division by which gametes, with
half the number of chromosomes, are produced.

• Diploid (2n)  haploid (n)

• Meiosis is sexual reproduction.

• Two divisions (meiosis I and meiosis II).

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Meiosis
• Sex cells divide to produce gametes (sperm or
egg).
• Gametes have half the # of chromosomes.
• Occurs only in gonads (testes or ovaries).
Male: spermatogenesis
Female: oogenesis

• Meiosis is similar to mitosis with some


chromosomal differences.

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Spermatogenesis
n=23
human
sex cell
sperm
n=23
n=23

2n=46
haploid (n)
n=23
diploid (2n) n=23

n=23

meiosis I meiosis II
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Interphase I
• Similar to mitosis interphase.

• Chromosomes replicate (S phase).

• Each duplicated chromosome consist of two


identical sister chromatids attached at their
centromeres.

• Centriole pairs also replicate.

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Meiosis I (four phases)
• Cell division that reduces the chromosome
number by one-half.

• four phases:
a. prophase I
b. metaphase I
c. anaphase I
d. telophase I

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Phases of Meiosis I

 The phases of Meiosis II are known as prophase II, metaphase


II, anaphase II and telophase II in meiosis II.
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 Similar to mitosis.
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