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HMM/SCM1414-Biology 1
CHAPTER 4CELL DIVISION
Cell division - continuity of life.
Functions of cell division:
(i) Reproduction
Division of unicellular organism
reproduces an entire organism.
Division on a larger scale produces
progeny for some multicellular
organisms.
(ii) Growth
Enables multicellular organism todevelop from single fertilized egg or
zygote.
(iii) Repair
In multicellular organism - repair and
renew cells that die from normal wearand tear or accidents.
Cell division is part of cell cycle - life of
cell from its origin in the division of a
parent cell until its own division into two.
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4.1 Chromosomes4.1.1 Chromosome number
Cell division requires distribution of
identical genetic material (DNA) to two
daughter cells.
Dividing cell duplicates its DNA,
allocates two copies to opposite ends of
cell, and then splits into two daughter
cells.
Genome the complete complement ofan organisms genes/an organisms
genetic material.
Prokaryotes usually, a single long DNA
molecule.
Eukaryotes - several DNA molecules.
DNA molecules are packaged into
chromosomes. Every eukaryote has characteristic
number of chromosomes in each cell
nucleus.
Diploidtwo sets (2n) ofchromosomes per cell, example somatic
cells.
Haploid having one set (n) ofchromosomes per cell, example
gametes.
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Human somatic cells - 46
chromosomes, made up of two sets of
23 (one from each parent).
Human gametes one set of 23
chromosomes.
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4.1.2 Structure of eukaryoticchromosomes
(a) Composition of Chromosome Eukaryotic chromosomes are made of
chromatin, a complex of DNA andassociated protein.
Chromosome
DNA Protein (Some RNA)
40%
Long,double
stranded (duplex)
150 million (1.5 X108) nucleotide pairs
Each chromosome
carries hundreds or
thousands of genes,
unit that specify an
organisms inherited
traits.
Length 4cm
(coiled to fit into
nucleus)
60%
histones
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Left- illustration of unfolded chromatin, right-micrograph of unfolded chromatin.
(b) Chromosome Coiling DNA (200 nucleotides) coiled around
core of8 histones to form nucleosome . Histones positively charged.
Have basic amino acids (arginine and
lysine). Attracted to phosphates (negatively
charged).
Different charges between DNA and
histones promote and guide coiling of
DNAsupercoils.
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Maintains structure of chromosome and
help control gene activity
Chromosome in non-dividing cell -
long, thin chromatin fiber.
Before cell division, chromatin
condenses, coils, and folds into
smaller package.
Heterochromatin Highly condensed part of DNA.
Not transcribed into mRNA.
Genes/DNA inactive/not expressed.
Euchromatin: Only condensed during cell division.
At other times open/not tightly packed.
Transcribed into mRNA.
Genes/DNA active/expressed.
(c) Chromosome Karyotypes A display of an individuals
homologous chromosomes/
chromosomes of an organism,
arranged by shape and size.
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Varies among:
(i) Species
(ii) Individuals of same species.
Homologous chromosomes(homologues ):
Members of a chromosome pair
having similar shape (structure) and
same sequence of genes along their
length/ Two copies of each chromosome
in body cells which have similar shape
& same sequence of genes along their
length. Each duplicated chromosome consists of
two sister chromatids, each containingidentical copies of chromosomes DNA,
joined at centromere.
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Centromere point of constriction ofchromosome containing specific DNA
sequence (condensed area).
Kinetochore disk of protein whichfunctions as attachment site for fibers
assist in cell division.
Later in cell division, sister chromatids
are pulled apart & repackaged into two
new nuclei at opposite ends of parent
cell.
Once separate, they are considered
individual chromosomes.
Sister chromatid
Chromosome
Homologous chromosome
KinetochoreCentromere
Spindle microtubule
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4.2 The Cell Cycle Repeating sequence of growth and
division through which cells pass each
generation.
4.2.1 Phases of cel l cycle(Refer to Figure 12.5, Campbell, pages 221)
Mitotic (M) phase of cell cycle alternateswith interphase. M phase - mitosis + cytokinesis. Interphase - 90% of cell cycle.
Three subphases ofinterphase:
(i) G1 phase (first gap)(ii) S phase (synthesis)(iii) G2 phase (second gap). During these subphases, cell grows by
producing proteins & cytoplasmic
organelles such as mitochondria & ER.
But chromosomes are duplicated only
during S phase. Daughter cells may then repeat cycle.
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Cell Cycle
Interphase Mitosis
(M)
Cytokinesis
(C)
G1 S G2
Summary:
Phase Events within cell
G1 Intensive cellular synthesis & cell growthoccurs.
Mitochondria, chloroplasts, ER, lysosomes,Golgi apparatus &vesicles produced.
NucleolusproducesrRNA. mRNA andtRNA.
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& chloroplast divide. Energy storeincreased. Mitotic spindle begins to
form.
M Nuclear division occurs in four phases.
C Equal distribution of organelles &
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cytoplasm to each daughter cells.
4.2.2 Duration of the cell cycle Typical human cell divides once every 24
hours:
M phase: < 1 hour S phase: 1012 hours (half the cycle)
G1 & G2: Remainder - divided between the 2
phases.
G1 varies most in length from cell to cell.
Duration of cell cycle varies:
Fruit fly 8 minutes.
Growing embryo cell 20 minutes.
Human liver cells - > 1 year.
Variation in length of cycle occurs in G1
phase.
Sometimes cells pause/are arrested in G1
phase and enters resting phase (G0). May remain for days, years, or
permanently until a suitable condition.
Examples:
(a) Muscle & nerve cells remains
permanently in G0 phase. Thus,
damaged cellscannotbe replaced
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(b) Liver cells resume G1 phase in
response to injury.
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4.3 Mitosis and Meiosis4.3.1 Outline of Mitosis(Refer to Figure 12.6, Campbell, pages 222 223)
(a) Late Interphase (G2) Chromosomes duplicated but are not
condensed.
Nuclear membrane bounds the nucleus -
contains one or more nucleoli. Centrosome replicated to form two
centrosomes.
In animal cells, each centrosome has two
centrioles.
(b) Prophase Chromosomes tightly coiled, with sisterchromatids joined together. Nucleoli disappear.
Mitotic spindle begins to form.
Composed ofcentrosomes andmicrotubules that extend from them.
Radial arrays of shorter microtubules that
extend from centrosomes are called
asters.
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Centrosomes move away from each other,
propelled by lengthening microtubules.
(c) Prometaphase Nuclear envelope disintegrates, and
microtubules from spindle interact with
condensed chromosomes.
Each of two chromatids of a chromosome
has a kinetochore located at centromere. Kinetochore microtubules from each pole
attach to one of two kinetochores.
Non-kinetochore microtubules interact with
those from opposite ends of spindle.
(d) Metaphase Longest stage (20 minutes)
Spindle fibers push sister chromatids untilthey are all arranged at metaphase plate,an imaginary plane equidistant from poles,
defining metaphase.
Centrosomes on opposite poles.
Kinetochores of sister chromatids attached
to kinetochore microtubules coming fromopposite poles.
(e) Anaphase Shortest stage.
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Centromeres divide, separating sister
chromatids each chromatid becomes a
chromosome.
Each is now pulled toward pole to which it
is attached by spindle fibers.
By the end, two poles have equivalent
collections of chromosomes.
(f) Telophase Genetically identical daughter nuclei beginto form at two poles.
Nuclear envelopes arise from fragments of
parent cells nuclear envelope and other
portions of endomembrane system.
Chromosomes become less tightly coiled.
(g) Cytokinesis Cytokinesis is usually well underway by
late telophase.
In animal cells, cytokinesis involves
formation of a cleavagefurrow, which
pinches cell in two.
In plant cells, vesicles derived from Golgi
apparatus produce cell plate at middle of
cell.
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4.3.2 Outline of Meiosis(Refer to Figure 13.8, Campbell, pages 244 245)
Meiosis I(a) Prophase I Occupies > 90% of time required for meiosis. Five stages:
Leptotene Chromosomes coil/condense tightly.
Homologous chromosomes looselypaired & aligned gene by gene.
(ii) Zygotene Pairing ofhomologous chromosome,
forming tetrad/bivalent - a group offour chromatids.
One/more chiasmata per tetrad.
Synapsis synaptonemal complexforms between homologous
chromosomes holds chromosome
togetheralong their lengths, precisely
aligning gene by gene.
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A B
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(iii) Pachytene Synapsis completed synaptonemal
complex enables crossingoverbetween homologous chromosomes.
(iv) Diplotene Homologues repel each other.
Chiasma Formation: X-shaped structure under light
microscope.
Evidence of crossing over- DNA in
non-sister chromatids break at
particular portion and rejoin to the
other DNA.
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A B
Chiasma
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Synaptonemal complex
disassembled.
Chromosomes decondense active
in transcription.
(v) Diakinesis Bivalent moves to nuclear membrane.
Nuclear membrane breaks down.
Transcription stops.
Chromosomes recondense.
Also: movement of centrosomes,
formation of spindle microtubules, and
dispersal of nucleoli.
Late prophase I: kinetochores of each
homologue attach to microtubule from
one pole to another.
Homologus pairs move towards metaphase
plate.
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(b) Metaphase I Tetrads arranged at metaphase plate, with
one chromosome facing each pole.
(c) Anaphase I Homologous chromosomes separate &
move toward each pole.
Sister chromatids remain attached at
centromere & move as single unit toward
pole.
(d) Telophase I & Cytokinesis Occur simultaneously.
Movement of homologues continues until
there is haploid set at each pole.
Each chromosome has two sister
chromatids.
Cytokinesis forms two haploid daughter
cells.
Animal cells - cleavage furrow.
Plant cells - a cell plate.
No chromosome replication between end ofmeiosis I and beginning of meiosis II.
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Meiosis II Meiosis II is very similar to mitosis.
(a) Prophase II Spindle apparatus forms and attaches to
kinetochores of each sister chromatid.
Spindle fibers from one pole attach to
kinetochore of one sister chromatid, and
those of other pole attach to kinetochore of
other sister chromatid.
Chromosomes (two chromatids each) move
to metaphase II plate.
(b) Metaphase II Sister chromatids are aligned at
metaphase plate.
Sister chromatids of each chromosome no
longer genetically identical due to crossing
over.
Kinetochores of sister chromatids attach
to microtubules extending from opposite
poles.
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(c) Anaphase II Centomeres of sister chromatids separate
and two newly formed individual
chromosomes travel toward opposite poles.
(d) Telophase II and Cytokinesis Chromosomes arrive at opposite poles.
Nuclei form around chromosomes, which
begin decondensing, and cytokinesis
separates the cytoplasm.
At the end of meiosis, there are four
haploid daughter cells.
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Key differences between mitosis and meiosis:
1. Chromosome number
Meiosis - reduced to haploid.
Mitosis conserved (diploid).2. Daughter cells
Meiosis - genetically distinct from parent
cell and from each other.
Mitosis genetically identical to parent
and to each other.
Three events unique to meiosis:1. Prophase I synapsis & crossing over. None
in mitosis.
2. Metaphase I - homologous pairs of
chromosomes align along metaphase plate.
Mitosis - individual replicated chromosomes.
3. Anaphase I - homologous chromosomes
separate & are carried to opposite poles ofcell. Mitosis - sister chromatids separate to
become individual chromosomes.
Meiosis I = reductional division
Number of chromosome sets per cell is
halved - reduction from diploid to haploid
state. Sister chromatids separate during meiosis
II.
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4.4 Control of Cell Cycle Timing and rates of cell division are crucial
for normal growth, development, and
maintenance.
Cell cycle is driven by specific chemical
signals present in cytoplasm.(Refer to Figure 12.13, Campbell, pages 228)
Evidence: experiments - cultured
mammalian cells at different phases of cellcycle were fused to form a single cell with
two nuclei.
(i) Fusion of S phase cell and G1 phase cell
induces G1 nucleus to start S phase.
Chemicals present in S phase nucleus
stimulated the fused cell.(ii) Fusion of cell in mitosis (M phase) with
cell in interphase (even G1 phase)
induces the second cell to enter
mitosis.
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4.4.1 Component of Cell Cycle ControlSystem
Sequential events of cell cycle are directed
by a cell cycle control system. Cyclically operating molecules that
trigger and coordinate key events in
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 is achieved?
(i) Internal clock
Each phase allocated adequate time to
finish.
Disadvantage:not flexible more time
may be needed.
(ii) Let each phase be completed first
before proceeding to next phase.
Control system in eukaryotic cells is a
centralized control system called
checkpoints. A critical control point where stop and
go-ahead signals can regulate the cycle/a
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regulated transition in cell cycle where
progression to 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.
The cell cycle is regulated at checkpoints by
external and internal controls. Three major checkpoints are found in the
G1, G2, and M phases.
(Refer Figure 12.14, Campbell, page 229)
(i) G1 checkpoint (G1/S checkpoint): Called restrictionpoint in mammalian
cells. If cell receives a go-ahead signal, itwill 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 isarrested/paused by G1 checkpoint if:
(a) Environmental condition (internaland external signals) not conducive to
cell division.
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Internal signals - nutritional state and
size of the cell.
External signals - factors that promote
cell growth and division.
(b) Cell goes into extended G0 phase
(non-dividing state).
Most cells in human body are in this
phase.
Liver cells can be called back to the
cell cycle by external cues, such as
growth factors released during injury.
Highly specialized nerve and muscle
cells never divide.
(c) Check damage of DNA(ii) 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 insufficient cell size.
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(iii) M checkpoint (M/G1 checkpoint) /spindlecheckpoint:
Determines whether cycle can exit
from mitosis/enter G1 phase by assessing
mitosis (the metaphase-to-anaphase
transition).
Cycle arrested if spindle not fully
assembled or other preparations for
mitotic exit are not complete.
Ensures that all chromosomes are
present at metaphase plate.
4.4.2 Mechanism of Cell Cycle Control Cell cycle checkpoints monitored by 2
regulatory proteins which are sensitive toconditions of cell:
(1) Cyclin-dependent protein kinases(Cdks) (known as kinases in inactiveform)
(2) Cyclins Cdks are enzymes that activate or deactivate
other proteins components necessary for
mitosis by phosphorylating them (example:
histones & mitoticspindle proteins)
Cyclinbinds to and activate Cdk
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Detailed molecular mechanisms thatregulate cell cycle.(See Figure 12.16b, Campbell, page 230)
1. During G1, cyclin is degraded, Cdk
component of MPF is recycled (inactive
form).
2. In late S phase, cyclin is synthesized and
accumulated through G2.
3. Cyclin moleculescombine with Cdk
molecules producing enough MPF to pass
the G2 checkpoint and initiate mitosis.
4. MPF promotes mitosis by phosphorylating
proteins. (Example, phosphorylation of
various proteins of nuclear lamina which
promotes fragmentation of nuclear
envelope during prometaphase). Its activity
peaks during metaphase.
5. During anaphase, cyclin is degraded,
terminating M phase. Cell enters G1 phase.
At least three Cdk proteins and several
cyclins regulate G1 checkpoint.
Similar mechanisms also involved in driving
cell cycle past M phase checkpoint.
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Internal and external signals helpregulate the cell cycle1. Internal signal
Example: M phase checkpoint ensures
all chromosomes are properlyattachedto
spindle at metaphaseplate before
anaphase.
Ensures daughter cells do not end upwith missing/extra chromosomes.
2. External signal: chemical and physicalfactors
Example: Cells fail to divide if an
essential nutrient is absent.For example, platelet-derived growth
factors (PDGF), produced by platelet
blood cells, bind to tyrosine-kinase
receptors of fibroblasts.
This triggers a signal-transduction
pathway that allows cells to pass G1
checkpoint and divide.
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At least 50 different growth factors can
trigger specific cells to divide.
4.4.2 The Cell Cycle and Cancer Cancer the unrestrained/uncontrolled
growth of cells failure of cell cyclecontrol.
Caused by Guardian Angel gene, p53 plays important role in G1 checkpoint.
Genes product is the protein, p53.
Checks whether DNA has successfully
replicated & is undamaged.
IfDNA is damaged, p53 halts cell division
and stimulate special enzymes (DNA
repair enzyme) to repairit.
Once repaired, p53allows cell division to
proceed.
Because p53halts division of damaged cells,
p53is considered to be tumor suppressorgene.
IfDNA cant be repaired, p53directs the cell
to kill itself= apoptosis(cell suicide) toprevent development of many mutated cells.
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p53is absent or damaged (nonfunctional/
defective) in cancerous cells undergo
repeated cell division without being halted at
G1 checkpoint.
Cancer cells divide excessively and invade
other tissues because they are free of bodys
control mechanisms.
Cancer cells do not stop dividing when
growth factors are depleted because they:
(i) manufacture their own growth factors
(ii) have abnormality in signaling pathway
(iii) have abnormal cell cycle control
system.
If and when they stop dividing, they do so
at random points, not at normal checkpoints
in cell cycle.
May divide indefinitely if they have a
continual supply of nutrients.
May be immortal.
Example: HeLa cells from a tumor removed
from a woman (Henrietta Lacks) in 1951
are still reproducing in culture.
Their abnormal behavior begins when a
single normal cell in a tissue undergoes
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transformation that converts it to a cancercell.
Normally, immune system recognizes and
destroys transformed cells.
However, cells that evade destruction
proliferate to form tumor, a mass ofabnormal cells.
If abnormal cells remain at originating site,
lump is called a benign tumor. Most do not cause serious problems and
can be fully removed by surgery.
In malignant tumor, cells becomeinvasive enough to impair functions of one or
more organs.
Abnormality of cells of malignant tumors:
1. Excessive proliferation.
2. Unusual chromosome number.
3. Metabolic abnormalities - may be disabled,
and may cease to function in
constructive way.
4. Often lose attachment to nearby cells &
are carried by blood and lymph system
to other tissues, and start more tumors
in an event called metastasis.
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5. May secrete signal molecules that cause
blood vessels to grow toward tumor.
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Carcinogens(cancer-causing agents) -cigarette smoke, ultraviolet radiation, X-ray,
and more than 1,000 known chemicals,
including numerous pesticides, householdproducts, and food additives causes
mutation ofp53genes.
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Tumor
(Latin = any swelling)
Inflammation
(Redness & swelling
with heat & pain)
Neoplasia
(Abnormal new
growth)
Benign
Growth usually
slow, localized
and/or encapsulated
Malignant
(Cancer)
Growth often rapid,
disorganized, not
confined invades and
replaces or destroys
adjacent tissues;
metastasizes.
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Proto-oncogenes: genes that normallypromote cell division.
Oncogenes: mutated form of proto-oncogenes that causes unrestrained cell
growth and division.
Tumor-suppressorgenes: Genes thatnormally inhibits cell division, but when
mutated, fail to keep a cancer from growing.
Treatments for metastasizing cancers:(i) High-energy radiation
(ii) Chemotherapy with toxic drugs.
These treatments target actively dividing
cells.
Chemotherapeutic drugs interfere with
specific steps in cell cycle. For example, Taxol prevents mitotic
depolymerization, preventing cells from
proceeding past metaphase.
Side effects of chemotherapy are due to
drugs effects on normal cells.