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4.

0 CELL DIVISION ( THE CELL CYCLE, Campbell)

 All species of organisms grow and reproduce.


 Cells of organism divide in order to grow and
reproduce.
 A dividing cell duplicates its DNA, allocates the two
copies to opposite ends of the cells and splits into
daughter cells.
 Both prokaryote and eukaryote will form 2 daughter
cells by the end of cell division, each with the same
genetic information.
 The genetic material (hereditary information) (DNAs)
is passed to their offspring via reproduction.
 The DNAs are collectively called the organism’s
genome

4.1 CHROMOSOMES

4.1.1 CHROMOSOME NUMBER

Number varies. (Refer Figure 15.5, page 299,


Biology, 7th Edition by Solomon).
Each chromosome contains thousand of genes.
Thus, ALL chromosomes are essential for survival.
Example:
 Lack one chromosome: 45 (monosomy) – does not
survive embryonic development.
 Extra one chromosome: 46 (trisomy) – fatal/only a
few survive but with problems, example, Down
syndrome (extra chromosome number 23).

Diploid – having two sets of chromosomes per cell


= 2n.
Haploid – having one set of chromosomes per cell
=n
Example – human cells:
 2n = 46 – somatic cells/body cells.
 n = 23 – gametes (egg/ovum and sperm).
 Each set contains 23 chromosomes.
 (Human liver cells – 2 nucleus; Red blood cells –
no nucleus).
4.1.2 STRUCTURE OF EUKARYOTIC CHROMOSOMES

(a) Composition of Chromosome


Chromosome

DNA Protein (Some RNA)

• 40% 60%
• Long, double stranded Histones
(duplex)
• 150 million (1.5 X
108)nucleotide pairs
• Length ≈ 4cm (coiled to
fit into nucleus)page
360, Biology,7th Edit.,
Campbell.

Left- illustration of unfolded chromatin, right- micrograph of


unfolded chromatin (looked like a string of beads).
(b) Chromosome Coiling
(Refer Figure 9.4, page 177, Biology, 7th Edition by
Solomon, refer to figure 19.2, page 361, Biology, 7th
Edition by Campbell ).

DNA (200 nucleotides) coiled around core of 8


histones to form nucleosome.
Histones positively charged.
 Have lots of basic amino acids (arginine and
lysine).
 Attracted to phosphates( negatively charged).
 Different charges between DNA and histones
promote and guide the coiling of DNA
supercoils.
Heterochromatin:
 Highly condensed part of DNA.
 Not transcribed into mRNA.
 Genes/DNA is inactive/not expressed.
Euchromatin:
 Only condensed during cell division.
 At other times – open/not tightly packed.
 Transcribed into mRNA.
 Genes/DNA are active/expressed.

(c) Chromosome Karyotypes


 A display of an individual’s homologous
chromosomes/chromosomes of an organism,
arranged by shape and size.
 Varies among:
(i) Species
(ii) Individuals of same species.

Homologous chromosomes (homologues):


 Members of a chromosome pair which have the a
similar shape (structure) and the same sequence
of genes along their length/ Two copies of each
chromosome in body cells which have a similar
shape and same sequence of genes along their
length.
 Each chromosome has two identical sister
chromatids joined at the centromere.
Homologous chromosome

Sister chromatid

Spindle microtubule

Centromere Kinetochore

Chromosome
• Centromere – point of constriction of the
chromosome containing specific DNA sequence
(condensed area).
• Kinetochore – disk of protein which functions as
attachment site for fibers → assist in cell division.
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4.2 THE CELL CYCLE

 The repeating sequence of growth and division


through which cells pass each generation.

4.2.1 THE PHASES OF CELL CYCLE

Cell Cycle

Interphase Mitosis Cytokinesis


(M) (C)

G1 S G2

Summary:
Phase Events within cell
G1  Intensive cellular synthesis & cell growth
occurs.
 Mitochondria, chloroplasts, ER,
lysosomes, Golgi apparatus & vesicles
produced. Nucleolus produces rRNA.
mRNA and tRNA.
 Cell produces structural and functional
proteins.
 Substances produced to inhibit or
stimulate onset of next stage.
S  DNA replication.
 Histones synthesized and wind each DNA
strand.
 Each chromosome has become two
chromatids.

G2  Intensive cellular synthesis. Mitochondria

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& chloroplast divide. Energy store


increased. Mitotic spindle begins to form.
M Nuclear division occurs in four phases.
C Equal distribution of organelles & cytoplasm
to each daughter cells.

4.2.2 DURATION OF CELL CYCLE

o Duration of cell cycle varies:


 Fruit fly – 8 minutes.
 Growing embryo cell – 20 minutes.
 Typical rapidly dividing mammalian cell – 24 hours.
 Human liver cells - > 1 year.
o Variation in length of cycle occurs in the G1 phase.
o Sometimes cells pause/are arrested in G1 phase and
enters the resting phase (G0).
o Cells may remain in G0 phase for days, years, or
permanently until a suitable condition.
Examples:
 Muscle & nerve cells – remains permanently in G0
phase therefore damaged cells cannot be replaced
 Liver cells – resume G1 phase in response to
injury.

4.3 MITOSIS AND MEIOSIS

4.3.1 OUTLINE OF MITOSIS

(a) INTERPHASE

G1: Active growth phase.


S:
 Chromosome replicates → 2 sister chromatids.
 Chromosome fully extended & uncoiled – invisible
under the light microscope.

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G2 :
 Chromatin fibres condensed → coil more tightly.
 Micotubular apparatus assembled (to move
chromosome to opposite poles of cell).
 In animal cells – centriole replicates forming
centrosome.. (None in plants)

(b)PROPHASE
Chromosomes are visible due to high degree of
coiling and condensing of chromatin fibres.
In animal cells: centrioles pair move apart, mitotic
spindles formed between them.
Centrioles produce asters (shorter microtubules
facing the plasma membrane), anchors centrioles to
plasma membrane.

(d) PROMETAPHASE

Nuclear envelope breaks down.


Microtubules extend from each centrosome toward
the middle of the cell, attach to kinetochores on each
pair of sister chromatids (linking sister chromatids to
opposite poles)
Non-kinetochore microtubules interact with those
from the opposite pole.

(d)METAPHASE

Chromosome aligns in circular array in


center/equator of cell (metaphase plate).

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(e)ANAPHASE

Shortest phase (but most spectacular).


Centromeres divide, move towards poles.
Sister chromatids separated and pulled towards
different poles.
Cell elongates.
Two ends of the cell have equivalent and complete
collection of chromosomes.

(f)TELOPHASE

Spindle apparatus disassemble.


Microtubules broken down.
Nuclear envelope forms around chromosomes.
Nucleolus reappears.

CYTOKINESIS

Cells form a cleavage furrow which pinches the cell in


two/equal halves.

(a) Cytokinesis in animal cells

Actin filament belts constrict at equator of cell.


Cleavage furrow forms around cell’s circumference.
Furrow depends/pinches inward → cell divides into 2.

(b) Cytokinesis in plant cells

Cell plates assembled in interior of cell.


Plates grow inward, reach plasma membrane and
fuse.
Cellulose added → new cell wall formed.

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Space between daughter cell → middle lamella.

4.3.2 OUTLINE OF MEIOSIS

(a) Interphase

Same as in interphase of mitosis.

(b) Prophase 1

Chromosomes begin to condense,


In synapsis, synaptonemal complex formed
between homologues, holding them tightly along
their lengths.
The chromosome pair appear as tetrad
Kinetochores of each homologue attach to
microtubules from one pole.
The homologous pairs then move toward the
metaphase plate.

Five stages: leptotene, zygotene, pachytene,


diplotene, and diakinesis.
(Refer Figure 12.9, page 232, Biology 5th Edition,
Raven & Johnson)

Leptotene:
 Chromosomes coil/condense tightly. Homologous
chromosomes are loosely paired aligning gene by
gene.

Zygotene:
 Homologous chromosome in the pairing process
(forming tetrad/bivalent// a group of four
chromatids), each tetrad has one or more
chiasmata.

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 Synapsis – synaptonemal complex formed


between homologous chromosomes → holds
chromosome together along their lengths.

Pachytene: A B
 Synapsis completed – synaptonemal complex
enables crossing over between homologous
chromosomes.

A B
Diplotene:
 Homologues are repelling each other
 Chiasma appear
 Chiasma Formation: (Plural – chiasmata)
 X-shaped structure as seen under
light microscope.
 Evidence of crossing over. DNA molecules in

Chiasma

nonsister chromatids break at particular portion


and rejoin to the other DNA .
 Synaptonemal complex disassembled.
 Chromosomes decondense → active in
transcription.

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Diakinesis
 Bivalent moves to nuclear membrane.
 Nuclear membrane begins to break down.
 Transcription stops.
 Chromosomes recondense.

(c) Metaphase 1

Pairs of homologous chromosomes arranged on the


metaphase plate.

(d) Anaphase 1

Sister chromatids remain attached at the


centromere and move as a single unit toward
the same pole.
Homologous chromosomes move toward
opposite poles.

(e) Telophase 1 and cytokinesis

Both occur simultaneously. Other events are the


same as in Telophase and cytokinesis of mitosis.
Each daughter cell has haploid set of
chromosomes but each chromosome still
composed of two sister chromatids.
There is no replication between meiosis 1 and
meiosis II.

(f) Prophase 11

Spindle apparatus reformed.

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Chromosomes ( composed of two sister


chromatids) move toward the metaphase II
plate.

(g) Metaphase 11

Chromosomes aligned on the metaphase plate.


Kinetochores of sister chromatids attach to
microtubules extending from the opposite poles.

(h) Anaphase 11

Centromeres separate.
Sister chromatids separate and each chromatid
move as a chromosome toward different /
opposite pole.

(i) Telophase 11 and cytokinesis

Chromosomes decondensed.
Nuclear envelope reformed.
Four daughter cells, each with haploid set and
different genetic material, are produced.

4.4 CONTROL OF CELL CYCLE

4.4.1 COMPONENT OF CELL CYCLE CONTROL


SYSTEM

Cell cycle control system is a cyclically operating set


of molecules in the cell that triggers and coordinates
key events in the cell cycle.
Aim of control system: To adjust duration of cycle so
that there will be enough time for all events to occur.
How it could be achieved?

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(i) Internal “clock”


 Each phase is allocated adequate time to finish
each phase.
 Disadvantage: not flexible – more time may be
needed.
(ii) Let each phase be completed first before
proceeding to next phase.
The control system used in eukaryotic cells is a
centralized control system called checkpoints.
The cell cycle is regulated at those checkpoints by
external and internal controls.
 Checkpoint –a critical control point where stop
and go-ahead signals can regulate the cycle.
/ a regulated transition in the cell cycle where
progression to the next phase depends on feedback
from the cell.
 Example: Feedback from cell about size or
conditions of cells can trigger or delay cell
proceeding to next phase of cycle.( Solomon)

Three checkpoints:

(Refer Figure 11.16, page 219, Biology 7th Edition,


Raven & Johnson, refer page 229, Biology 7th Edition,
Campbell.)
G2
checkpoint

M
checkpoint

G1
checkpoint

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G1 checkpoint (G1/S checkpoint):


 Called restriction point in mammalian cells. If a cell
receives a go-ahead signal, it will usually complete
the S, G2 and M phases.
 Decides whether cell should divide, delay division,
or enter resting phase (G0 phase) by assessing
progress/growth of cell.
 In eukaryotes, cell cycle is arrested/paused by G1
checkpoint if:
(i) Environmental condition (internal and external
signals) not conducive to cell division. Internal
signals (nutritional state and size of the cell).
External signals (factors that promote cell
growth and division)
(ii) Cell goes into extended G0 phase.
(iii) Check damage of DNA

G2 checkpoint (G2/M checkpoint):


 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 incomplete
DNA replication, DNA damage, and possibly by
insufficient cell size.

M checkpoint (M/G1 checkpoint) /spindle


checkpoint:
 Determines whether cycle can exit from
mitosis/enter G1 phase by assessing mitosis (the
metaphase-to-anaphase transition).
 Cycle is arrested if spindle is not fully assembled or
other preparations for mitotic exit are not
complete.

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 Ensures that all chromosomes are present at the


metaphase plate.

4.4.2 MECHANISM OF CELL CYCLE CONTROL

Molecular mechanism that regulates cell cycle

(Refer Figure 9-10, page 183, Biology 7th edition,)


Solomon
(Figure 11.18, page 221, Biology 7th edition, Raven &)
Johnson)

Cell cycle checkpoints are monitored by 2 regulatory


proteins which are sensitive to conditions of the cell:
(1) Cyclin-dependent protein kinases (Cdks)
( basically known as kinases in inactive form)
(2) Cyclins
Cdks are enzymes that phosphorylate components
necessary for mitosis (example: histones & mitotic
spindle proteins)
Cyclin binds to and activate Cdk
 Synthesized and destroyed at each turn of cell
cycle.
 Different cyclins regulate different cell cycle
checkpoints.

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 Activity of Cdk rise and fall with the changes in the


concentration of its cyclin partner.

Working principle of cell cycle control


 Cyclin binds to Cdks to form a complex. The first
cyclin-Cdk complex discovered is MPF (mitosis
promoting factor
 If the cell detects some problems with the
continuation of the cycle, the activation of cyclin-
Cdk complex is not complete – cycle does not
proceed to next phase.
 If no defect is detected, the cyclin-Cdk complex is
activated by phosphorylation (addition of
phosphate to substrate protein).
 Cycle can proceed to the next phase - specific
genes for the next phase are transcribed including
transcription of next cyclin and kinase genes.

Detailed molecular mechanisms that regulate


cell cycle.
 During G1, cyclin is degraded, Cdk is recycled
(inactive form).
 In late S phase, cyclin is synthesized and
accumulated through G2.
 Sufficient MPF is formed to pass the G2 checkpoint
and initiate mitosis.
 MPF promotes mitosis by phosphorylating
proteins. Its activity peaks during metaphase.
 During anaphase, cyclin is degraded, terminating
M phase.

PDGF ( platelet-derived growth factor) is example of


important external factor that permits fibroblast to
pass G1 checkpoint and divide. In mammals, there

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are 50 types of growth factors to trigger the division


of different cells.

4.4.3 THE CELL CYCLE AND CANCER

(Refer Figure 11.24, page 222, Biology 7th Edition,


Raven & Johnson)

Cancer – the unrestrained/uncontrolled growth of


cells → failure of cell cycle control.
Cancer cells have the ability to invade surrounding
tissues.
Caused by “Guardian Angel gene”, p53 → plays
important role in G1 checkpoint.
The gene’s product is the protein, p53.
 Checks whether DNA has successfully replicated &
is undamaged.
 If DNA is damaged, p53 halts cell division and
stimulate special enzymes (DNA repair enzyme) to
repair it.
 Once repaired, p53 allows cell division to proceed.
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.

Carcinogens (cancer-causing agents) such as


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.

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Proto-oncogenes: genes that normally promote cell


division.
Oncogenes: mutated form of proto-oncogenes that
causes unrestrained cell growth and division.
Tumor-suppressor genes: a gene that normally
inhibits cell division, but when mutated, causes
unrestrained cell division.
Malignant –cells have ability to spread to other
parts of the body.
 An individual with malignant is said to have cancer.
 This spread of cancer beyond their original sites is
called metastasis.

Tumor
(Latin = any swelling)

Inflammation Neoplasia
(Redness & swelling with (Abnormal new growth)
heat & pain)

Benign Malignant
Growth usually slow, (Cancer)
localized and/or Growth often rapid,
encapsulated disorganized, not
confined – invades and
replaces or destroys
adjacent tissues;
metastasizes.

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