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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.

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HMM1414 Chapter 4

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