DNA Structure & Function

Deoxyribonucleic Acid
● Interpret experiments relating to DNA as the genetic material
○ Chargaff Ratio (1950) (complementary base pairing) → proportion of A:T and C:G is approximately 1:1 (consistent base pairing in DNA)
○ IMPORTANT: use experimental data and show that it sizes down to approximately 1:1!!

Nucleic Acids
known as the information molecules of cells; they are the genetic material of all living things and viruses
also known as the genetic code

There are 2 types of nucleic acids:

➢ DNA (deoxyribonucleic acid)
➢ RNA (ribonucleic acid)
❖ Nucleic acids are macromolecules (or polymers) because they are made by linking together smaller monomers, known as nucleotides
➢ remember that 1 → monomer, 2 → dimer, >3 → polymer
● Outline the relationship between DNA, genes and chromosomes.
○ DNA is the genetic material and occurs in the chromosomes of the nucleus
● State that
○ each gene is a sequence of nucleotides as part of a DNA molecule

● State the structure of DNA in terms of the bases, sugar and phosphate groups found in each of their nucleotides.

Nucleotide - the building blocks

A nucleotide consists of 3 components combined together:
● A nitrogenous base
○ CGAT (in DNA)
○ CGAU (in RNA)
● Pentose sugar (5-C)
○ Deoxy-ribose (in DNA)
○ Ribose (in RNA)
● Phosphate
Nitrogenous bases: derived from one of 2 parent compounds:
➔ Purine bases: Adenine (A) & Guanine (G)
➔ Pyrimidine bases: Cytosine (C) and Thymine (T)/ Uracil (U)

Nucleotides are formed through condensation reactions, with formation of

2 water molecules

- Label 5-C with numbers 1-5, clockwise

- Phosphate always linked to Carbon atom 5
- Nitrogenous base linked to Carbon atom 1

Formation of Dinucleotide - Phosphodiester bonds

 ● a phosphodiester bond is a COVALENT bond between the 5’ phosphate group of one nucleotide and the 3’ OH group of another nucleotide
● It is formed by a condensation reaction and a water molecule is lost in the process
Dinucleotide to Nucleic Acid
● occurs through condensation reaction between phosphate group of one nucleotide, and the sugar group of another nucleotide
● Alternating sugar and phosphate molecules form a backbone SUGAR-PHOSPHATE BACKBONE with one of the bases attached to each of the sugar
molecule along the strand confer (DNA STABILITY)
● Since the bases vary, they represent a unique sequence that carries coded information held by the nucleic acid
DNA
● A DNA molecule consists of 2 polynucleotide strands paired together. These strands are held by hydrogen bonds between paired bases and take
the shape of a double helix
● the pairing of bases is between A & T and G & C, because there is just enough space between the two sugar phosphate backbones for 1 purine and
1 pyrimidine
● 2 hydrogen bonds between A=T, 3 hydrogen bonds between CΞG. This is known as complementary base pairing. (DNA STABILITY)
● DNA strands are antiparallel. One chain runs from 5’ to 3’ while the other runs from 3’ to 5’.
 ● Describe and explain features that contribute to DNA stability
1. nucleotides are joined by phosphodiester bonds, which are strong covalent bonds, to form the sugar-phosphate backbone
2. Orientation of DNA strands are antiparallel and run in opposite directions, one from 3’ to 5’ and the other from 5’ to 3’. this
allows for complementary base pairing. hydrogen bonds are formed between complementary bases, although weak by itself,
hydrogen bonds provide support to the structure collectively
How is Genetic Material organised?
● Role of DNA is to instruct cells to make specific polypeptides and proteins
● In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes
● Each chromosome is made up of DNA coiled 1.75 times around a core of histone proteins
● A sequence of nucleotides makes up a gene and the sequence can vary. Each gene controls the formation of a single polypeptide, which determines
a phenotype.

The Meselson-Stahl Experiment

➔ 1958, Meselson and Stahl conducted an experiment to determine the mechanism of DNA replication

I. Form of bacteria was grown in a medium that only contained the heavy nitrogen isotope 15N for many generations. The DNA of the bacteria became entirely
heavy as a result.
Why nitrogen? DNA contains a nitrogenous base. *Can use any other element as long as it is present in the DNA.
Hypothetical models:
1. Conservative
1 strand serves as template
2. Semi-conservative
2 strands serve as template
3. Dispersive
Breaks and reforms

II. Meselson and Stahl next took some DNA from the bacteria and centrifuged it. [caesium chloride gradient centrifugation]
- Forms bands at position where density of DNA = gradient of caesium chloride
- DNA containing 15N is denser than 14N, hence it sinks to a lower position
III. Bacteria was then transferred to a medium of the normal light
isotope 14N. Therefore, new DNA synthesised by the cells were
now made of 14N.

IV. After 20 min, a sample was prepared for centrifugation. This was identified as ‘first generation’. After another 20 min, the ‘second generation’
was taken and so on.
Explain semi-conservative replication.
- Both the original / parental strands contain only heavy 32P, each 32P-strand served as the template for replicating a new / daughter 31P-strand
- If replication is semiconservative, in the first generation, the isolated DNA showed only one single band of intermediate density
- where each replicated hybrid DNA molecule was composed of one new / daughter 31P-strand and one parental 32P-strand.

DNA Replication
● Since DNA carries the genetic message, replication is an extremely accurate process
● Replication takes place in the nucleus during interphase, before nuclear division
● Strands of the double DNA helix are built up individually from free nucleotides
Separation of DNA Strands
1. DNA replication begins at the origin of replication
2. Helicase unwinds the double helix by breaking the hydrogen bonds between the
complementary base pairs in the parental strands.
3. Each parental strand acts as the template for the synthesis of a new DNA strand.

Synthesis of RNA primer

4. Primase attaches to the unwound chain and catalyses the synthesis of RNA primer to
provide free 3’OH ends for DNA Polymerase III.

Synthesis of new daughter strand(s)

5. DNA Polymerase III elongates the new daughter strand in the 5’ to 3’ direction by
catalysing phosphodiester bond formation between the incoming deoxyribonucleotides
and the free 3’OH end of the daughter strand.
6. Free deoxyribonucleotides are incorporated by complementary base pairing to the
parental DNA strands, with adenine to thymine and guanine to cytosine.
7. In a replication fork, the leading strand is synthesised continuously.
8. While the lagging strand is synthesised discontinuously to form Okazaki fragments.
9. RNA primers are removed and replaced by deoxyribonucleotides by DNA Polymerase I.
10. Nicks between the Okazaki fragments are filled in by DNA ligase by forming
phosphodiester bonds between Okazaki fragments.

Agarose Gel Electrophoresis

Nucleic acids are electrophoresed within a porous matrix or “gel”. Most commonly, the gel is cast in the shape of a thin slab, with wells for loading the
sample.
Gel is immersed within an electrophoresis buffer (provides ions to carry a current) and a buffer (maintains the pH at a relatively constant value).
➔ Nucleic acids have a consistent negative charge imparted by their phosphate backbone and migrate toward the anode.
➔ The gel itself is composed of either agarose or polyacrylamide, both of which serve as molecular sieves to separate DNA based on size.
➔ Fragments of linear DNA migrate through agarose gels with a mobility that is inversely proportional to their molecular weight (ie. the heavier, the
slower the migration, hence they travel a shorter distance than those with lighter weight)
 1. Loading Dye
● Contains dyes to track how ‘fast’ DNA is migrating across the agarose gel.
● Usually dyes of two different sizes and colours (eg. bromophenol blue, xylene cyanol)
● One dye is smaller than most/all DNA fragments, therefore will run as fast/faster than the smallest DNA fragments
● The other dye is large, and will migrate along with the larger DNA fragments
● DNA sample is somewhere between the dyes, so when small dye gets near the end of the gel, the gel is stopped.
● Glycerol to render DNA samples (in aq solution hence same density as buffer) denser than the running buffer such that the DNA samples
will sink into the well.
2. DNA Ladder
● Different DNA molecules can be quantified in terms of their size.
● By using appropriate DNA molecular weight standards, the size )in base pairs) of the unknown DNA bands can be determined.

3. Nucleic Acid Dye

● In order to visualise DNA in gel electrophoresis, a dye has to be used to stain the agarose gel before/after electrophoresis.
● The nucleic acid dyes bind to DNA to form a complex, which can then be visualised by exposing the gel to UV or blue light.

Explain the principle of gel electrophoresis in the separation of these DNA fragments.
- Nucleic acids have a constant negative charge, and will migrate towards the anode under an electric current.
- The agarose gel acts as a molecular sieve to separate the DNA based on size.
- DNA fragments, which are longer/heavier molecular weight/mass will migrate slower and hence travel a shorter distance than those which are
shorter/lighter molecular weight/mass.

Cell Cycle, Mitosis & Meiosis

Cell Cycle
❖ Sequence of events that occur in between one division and the next
❖ 3 main stages:
➢ Interphase (G1, S and G2)
■ G → Gap phase (growth of organelles)
■ S → Synthesis (DNA replication)
➢ Nuclear Division (M)
■ M → Mitosis/Meiosis
➢ Cell Division (Cytokinesis)
■ Cyto → cell, kinesis → division

Interphase
G1: the ‘first gap’ phase The cell grows by producing proteins and cell organelles, including mitochondria and endoplasmic reticulum

S: synthesis - Growth of the cell continues as replication of DNA occurs.

- Protein molecules called histones are synthesised and attached to the DNA.
- Each chromosome becomes two sister chromatids.

G2: the ‘second gap’ phase - Cell growth continues by protein and cell organelle synthesis.
- Mitochondria and chloroplasts divide.
- The spindle begins to form.
Nuclear division, mitosis (M), follows.

Nucleus
● Largest organelle, 10-20㎛
● Contains chromosomes that are thread-like structures made up of
DNA and protein (histone), and are visible at the time the nucleus
divides. At other times, the chromosomes appear as a diffuse network
called chromatin.
● FUNCTION: Inherited genes on the DNA in the nucleus control protein
production and hence the activities of the cell

Importance & the role of the Nucleus

● The information in the nucleus is contained within structures called chromosomes. These uniquely:
○ Control cell activities
○ Are copied from cell to cell when cells divide
○ Are passed into new individuals when sex cells fuse together in sexual reproduction
The nucleus contains the chromosome of the cell, and the chromosomes contain the coded instructions for the organisation and activities of cells and for the
whole organism.
Chromosomes

● At the time a nucleus divides, the chromosomes become compact, much coiled structures - condensed state
● Chromosomes are very long, thin, uncoiled threads called chromatin at all other times
● Chromosomes hold the hereditary factors, genes. A particular gene always occurs on the same chromosome in the same position
● A single, enormously long DNA molecules runs the full length of each chromosome

Features of Chromosomes
 1) The shape of a chromosome is characteristic: they are of fixed length and with a
centromere somewhere along their length
❖ The centromere is always in the same position on any given chromosome
❖ The position of the centromere and length of a chromosome is how they are identified
in photomicrographs
2) The number of chromosomes per species is fixed
3) Chromosomes occur in pairs called homologous pairs; one of each pair came originally
from each parent
4) Chromosomes are copied (DNA replication) before nuclear division occurs, forming 2
identical sister chromatids attached at the centromere till separation and become
chromosomes again
*centromere is also DNA!

Packaging of DNA
● Each chromosome consists of a macromolecule of DNA in the form of a double helix
● About 50% of a chromosome is built of protein

Why is packaging necessary?

❖ Human DNA is over 2 metres long, shared out between 46 chromosomes.
❖ The condensed state of chromatin into chromosomes enables the safe storage of DNA
in nuclei
❖ And also allows access to selected lengths of DNA during transcription

Describe how DNA is packaged into a chromosome.

- DNA is coiled tightly many times around histone proteins.

Significance of Mitosis *does not occur in prokaryotes*

● Genetic stability
➢ Each daughter cell produced by mitosis has a full set of chromosomes, identical to those of the parent cell.
➢ No variation in genetic information therefore essential in
❖ Growth and development of embryo
❖ Replacement of damaged or worn out cells
 ❖ Asexual reproduction – as a consequence, the offspring have all the advantages of the parents in mastering the same habitat, and any
disadvantages too

Application question: explain why epithelial cells of the digestive system exhibit a higher rate of mitosis compared to the other cells of the body.
- Epithelial cells in the digestive system are constantly being damaged by friction and digestive juices.
- It is replaced through mitosis and therefore the epithelial cells have a higher rate of mitosis.

Mitosis
● Chromosomes, preset as sister chromatids formed during interphase, are separated and accurately and precisely distributed to two daughter nuclei
● A continuous process with no breaks in between the 4 phases: Prophase, Metaphase, Anaphase and Telophase

PROPHASE - 2n = 4 (but in this diagram is 3n = 6) / 2x METAPHASE - 2n = 4 / 2x

● Chromosomes increasingly shorten and thicken by supercoiling to become 2 sister

chromatids held together at the centromere ● Two centrosomes move to opposite ends of the cell
● Nucleolus gradually disappears, Nuclear envelope breaks down ● Microtubules of the cytoplasm start to form into a spindle, radiating
● DNA condenses out from the centrioles
● In animals, the centrosome (absent in plants) divides and the two centrioles ● Each pair of sister chromatids is attached to a microtubule of the
replicate (make copies) to form two centrosomes spindle and is arranged at the equator of the spindle/ metaphase plate

ANAPHASE - 4n = 8 (diagram on left) / 2x TELOPHASE - 4n = 8 (but this diagram 6n = 12) / 2x

● Centromeres separate ● Nuclear envelope reforms around both groups of chromosomes at
● Spindle fibres shorten opposite ends of the cell.
● Sister chromatids are pulled apart by centromeres to opposite poles ● Chromosomes ‘decondense’ by uncoiling, becoming chromatin again
○ Once separated, the sister chromatids are referred to as chromosomes ● Nucleolus reforms in each nucleus

Cytokinesis = Cytoplasm division

● Divisions of the cytoplasm, that follows interphase
● Cell organelles become evenly distributed between daughter cells
Animal cells Plant cells
Cytokinesis occurs by a process known as cleavage. The first sign of cleavage is the appearance Golgi apparatus forms vesicles of new cell wall materials which
of a cleavage furrow, a shallow groove in the cell surface near the old metaphase plate. In- collect along the line of the equator of the spindle = cell plate.
tucking of the cell surface membrane at the equator of the spindle, ‘pinching’ the cytoplasm in Vesicles will merge, forming new cell surface membranes and the
half. The cleavage furrow deepens until the parent cell is pinched into two, producing two cellulose cell walls between the two cells
separated cells

Summary of Mitosis
Mitosis results in two new daughter cells that are duplicates of the original parental cell (same number, same kind, hence genetically identical). One cell
with 46 chromosomes divides and becomes two cells with 46 chromosomes each. This kind of cell division occurs throughout the body, except in the
reproductive organs. This is the way most of the cells that make up our body are made and replaced.

Meiosis
– Homologous pair of chromosomes
❖ Matching pairs of chromosomes that can possess different versions of the same genes/alleles
❖ One member of the pair has come from the male parent and the other from the female parent
❖ These pairs are maintained by the exact replication that takes place prior to each mitotic division

longest → shortest | Karyotype: an individual’s collection of chromosomes

Haploid vs Diploid
 Haploid (n) Diploid (2n)

A eukaryotic cell or organism containing A eukaryotic cell or organism containing two

only one complete set of chromosomes complete sets of chromosomes (two copies of
(only one of each homologous each homologous chromosome)
chromosomes)
Eg. somatic cell (any cell in the body except
Eg. human sperm, secondary oocyte sperm & egg cells)

n=3 2n = 6

Meiosis = the Reductive Division

● A different type of nuclear division that results in daughter nuclei each containing half the number of chromosomes of the parent cell
● In sexual reproduction, two haploid cells (gametes) fuse (fertilisation) to form a diploid zygote which will grow and develop into a new individual
● Meiosis produces haploid gametes, which keeps the chromosome number from doubling each time sexual reproduction occurs (every
generation). When haploid gametes fuse the resulting cell has the diploid condition again.

PROPHASE I - 2n = 4 / 2x METAPHASE I - 2n = 4 / 2x
- 2 centrosomes start to move apart ● Spindle forms
- Nucleoli and nuclear envelope disappear ● Homologous pairs become attached to
● Synapsis: pairing of homologous chromosomes individual microtubules of the spindle by
● Crossing over between non-sister chromatids their centromeres
resulting in new combinations of genes on the OR ● Homologous pairs are arranged at the
chromosomes equatorial plate of the spindle framework
● Chiasma: point of the join between different variation ^^
chromatids (p. chiasmata)

ANAPHASE I - 2n = 4 / 2x TELOPHASE I - 2n = 4 / 2x
 ● Chromosomes of each homologous pair move to ● Homologous chromosomes arrived at opposite poles =
opposite poles of the spindle, but with the end of Meiosis I
individual chromatids remaining attached by their ● Chromosomes tend to uncoil
centromeres ● Nuclear envelopes reform around both nuclei
● Separation of homologous pairs of chromosomes ● Spindle breaks down
but NOT the sister chromatids ● These two cells do not go into interphase but continue
into Meiosis II directly

PROPHASE II - n = 2 / x METAPHASE II - n = 2 / x
● Nuclear envelope breaks down again ● Chromosomes line up at the equator of the spindle, attached
● Chromosomes shorten and re-thicken by coiling by their centromeres
● Centrioles (in animal cells only) duplicate and move
to opposite poles of the cell
● Spindle apparatus re-formed perpendicular to
original spindle

ANAPHASE II - 2n = 4 / x TELOPHASE II - 2n = 4 / x
● Nuclear envelopes form around the four
● Centromeres divide
groups of chromatids so four nuclei are
● Sister chromatids move to opposite poles
formed
of the spindle, centromeres first
● Chromosomes uncoil and become dispersed
as chromatin
● Nucleoli reform
● Followed by cytokinesis

Number of chromosomes (count centromeres)

Cytokinesis
 Meiosis & Genetic Variation
○ 4 haploid cells produced by meiosis differ genetically from one another because:
1) Independent assortment of maternal and paternal homologous chromosomes:
a) the way the chromosomes of each homologous pair line up at the equator of the spindle in meiosis I is entirely random
b) which chromosome of a given pair goes to which pole is unaffected by the behaviour of the chromosomes in other pairs
c) 223 = over 8 million possible combinations in human
2) The crossing over of segments of the individual maternal and paternal homologous chromosomes:
a) results in new combinations of alleles on the chromosomes of the haploid cells produced
b) generates unimaginable degree of variation / unlimited recombination
3) Fertilisation of male and female gametes in sexual reproduction
Recombination
● Offspring with combinations of characteristics different from their parents are called genetically varied
● Recombination in genetics is the combination of alleles or characters into different combinations from those of the parents
● Recombination occurs for:
○ Genes located on separate chromosomes by chromosome assortment in meiosis (unlinked genes)
○ Genes on the same chromosome by crossing over during meiosis (linked genes)
Summary of Meiosis
● Meiosis results in cells with half the number of chromosomes, 23, instead of the normal 46. This is the type of cell division that occurs in the
reproductive organs, resulting in the eggs and sperm.
Mitosis Meiosis

Nuclear division by mitosis occurs when Nuclear division by meiosis occurs when sexual
organisms grow and develop, and tissues are reproduction occurs (e.g. when gametes are formed
repaired or replaced. in mammals and plants)
 ● 2 daughter cells ● 4 daughter cells
● Same number of chromosomes as ● Half the number of chromosomes of parent
parent cell cell
● Genetically identical ● Genetically varied
● Diploid (2n) ● Haploid (n)
● Happens in somatic cells ● Happens in reproductive cells
● No crossing over/ pairing of homologs ● Crossing over & pairing of homologs
● Occurs when cells grow/ need to be ● Occurs when an organism reproduces
replaced/ an organism reproduces sexually
asexually

● Begin with one parent cell

● Have the same basic steps
● Create new cells
● Cells undergo DNA replication

Chromosomal Mutations
➢ Changes to the genome of the cell
○ A genome is the complete set of genetic information in an
organism.
➢ This may involve changes to the DNA sequence of the genes
➢ Chromosomal mutations may also arise due to:
○ Change in chromosomal number
○ Structural modification of chromosome
➢ Error in gametes, NOT in gene
➢ Can affect many genes in one go
The larger diagrams only show oocyte development. However, the sperm could
possibly be aneuploid, resulting in the possibility of a completely aneuploid embryo,
or polyploid, in which case triploid happens from the sperm.

Abnormal Number of Autosomes

Down Syndrome (Trisomy-21) ● Caused by trisomy in chromosome 21

● Trisomy: a condition arising when cells of an organism have 3 copies of a chromosome)
● Occurs in 1 out of 700 births
Patau Syndrome ● Trisomy 13
● Occurs in 1 out of 16,000 births
● Intellectual disability, physical abnormality, poorly developed eyes, cleft lip, polydactyly

Edward’s Syndrome ● Trisomy 18

● Second most common, after trisomy 21
● 1/5000 births
● Die before birth/within first month, clenched fists & overlapping fingers, abnormally shaped head, small jaw

Abnormal Number of Sex Chromosomes

Turner Syndrome ● Person only has one X chromosome (typically missing sex chromosome in sperm)
● Found only in women
● An example of monosomy in sex chromosomes
● 1/2500 births

Klinefelter Syndrome ● Trisomy of sex chromosomes

● Found in boys: XXY
● 1/750 births
● Half of cases: XX chromosomes from mother, other half: father’s sperm is XY

Cri-du-chat Syndrome (5p-syndrome) ● Deletion of short segment of chromosome 5

*structural but i lazy change ● 1/500,000 births
● Abnormal larynxes, weak muscle tone, high-pitched cries, delayed development

Change in Number of Chromosomes

● Nondisjunction can occur during meiosis I or II hence producing gametes with an incorrect number of chromosomes
● It is the failure of the two homologous chromosomes of a pair to separate to the opposite poles at anaphase I OR failure of sister chromatids to
separate at anaphase II
● If a normal gamete fertilises a gamete with an extra chromosome, the result is a zygote with a total of 2n + 1 chromosomes (aneuploidy;
condition in which an organism has one or a few chromosomes above or below the normal chromosome number)
● If the organism survives, it will have:
○ An abnormal karyotype
○ Probably a syndrome of disorders caused by the abnormal number of genes

What errors/chromosomal mutation happened during meiosis that lead to Trisomy 21?
- The chromosomal mutation is a nondisjunction.
- It is the failure of the pair of homologous chromosomes 21 to separate to the opposite poles at anaphase I or failure of sister chromatids of
 chromosome 21 to separate at anaphase II.
- If a normal gamete fertilises a gamete with an extra chromosome, the result is a zygote with a total of 47 chromosomes or 3 copies of
chromosome 21.

Structural Modification of Chromosome

1) Deletion
● Results from the breakage of a chromosome in which the genetic
material is lost during cell division
2) Duplication
● A major mechanism where new genetic material is generated,
resulting in extra genetic material
3) Inversion
● Rearrangement of the genes, where the broken segment is
inverted and inserted back onto the same chromosome
4) Translocation
● Abnormality caused due to rearrangement of parts between two
chromosomes. Piece of chromosome detaches itself and moves to
a new position on another chromosome

Cancer - diseases of uncontrolled cell divisions

● Cancer arises when the cell cycle operates without its normal controls - a molecular control system controlled by specific genes
● Rate of cell multiplication is very much faster than rate of cell death, and tumor is formed
○ Lump of cells → tumor (benign)
○ Spreading, out of control → cancer
Features of cancer cells
❖ Replicative immortality
Can divide many more times than a normal cell. In general, human cells go through 40-60 rounds of division before losing the capacity to divide, grow old
and die. Cancer cells divide many more times than this.
❖ Metastasis (malignant)
The ability to migrate to other parts of the body
❖ Angiogenesis
The ability to promote growth of new blood vessels, which helps provide tumor cells a source of oxygen and nutrients
❖ Immortal
Lost the ability to undergo apoptosis (programmed cell death) under conditions where normal cells would (due to DNA damage).
 ❖ Metabolic changes
Cancer cells undergo metabolic changes that support increased cell growth and division

Carcinogen
Ionising radiation Includes X-rays and radiation (gamma rays) from various radioactive sources. These may trigger formation of damaging ions
inside the nucleus

Non-ionising radiation Non-ionising radiations such as UV light. Less penetrating than ionising radiation, but if it is absorbed by the nitrogenous
bases of DNA, may cause DNA to bind to each other, instead of their partner on the opposite strand

Chemicals Several chemicals that are carcinogens present in tobacco smoke. Prolonged exposure to asbestos fibres may trigger cancer
in the linings of the thorax cavity.
● It is any agent that may cause cancer (eg. asbestos, tobacco smoke)
● Highly likely to cause damage to DNA molecules of chromosomes, resulting in mutation - a change in the amount or chemical structure of
chromosome
● Mutations of different types build up in the DNA of body cells over time
● A single mutation is unlikely to be responsible for triggering cancer
Causative factors that increase chances of cancerous growth
● Genetic
● Chemical carcinogens
● Radiation (x-rays, UV light)
● Loss of immunity
Why is there a need to regulate the mitotic cell cycle?
➢ Dysregulation of checkpoints of cell division can lead to uncontrolled cell division and cancer
➢ Loss of function mutation of tumor suppressor genes
➢ Gain of function mutation of proto-oncogenes (into ONCOGENE, which permanently switches on cell division)
Cancer as a multi-step process
● Accumulation of mutations (increased by carcinogens)
● Angiogenesis (stimulation of generation of new blood vessels that feed the tumor)
● Metastasis (spreading to other body parts)

Stem Cells
The Division of Cells
 Unicellular organisms → grow and divide in two under favourable conditions
Multicellular organisms → more complex
● Life begins as a single cell which grows and divides, forming many cells
● Some cells retain the ability to grow and divide throughout life to replace old or damaged cells
● Majority of the cells become specialised and most are unable to divide further
Stem Cell: A relatively unspecialised cell that can give rise to one or more types of specialised cells
➔ Have the unique ability to self-renew or differentiate into various cell types in response to signals within the body
➔ These properties provide stem cells with unique capabilities for tissue repair, replacement, and regeneration.
➔ They have become valuable research tools for regenerative medicine and other therapies.
Unique features of Stem Cells
1) Unlimited self-renewal capabilities
a) Able to continually divide and reproduce themselves for long periods
b) When cells replicate themselves many times over, it is called proliferation
2) Non-differentiated cells with unspecialised functions
a) Do not have tissue-specific structures to perform specialised functions
3) Can differentiate into specific cell types under appropriate conditions
a) Eg. stem cells in bone marrow differentiate to all kinds of blood cells
b) Eg. stem cells in adult brain produce certain kinds of nerve cells
Potency of Stem Cells
Totipotent cells ● Can form all cells types and placental cells in an organism
● Used to describe zygotes

Pluripotent cells ● Has potential to give rise to all cell types that make up the body of an organism
● Eg. embryonic stem cells

Multipotent cells ● Unspecialised cells that can differentiate into more than one cell type but are limited
● Eg. adult stem cells, cord blood stem cells can differentiate into different types of blood cells

Zygotic stem cells (TOTIPOTENT) Embryonic stem cells (ES cells) (PLURIPOTENT)
● Totipotent fertilised egg has the potential to give rise to all ● Can give rise to all the specialised cells in the body, almost any cell type of an organ
cell types and placental cells in an organism (except placenta and umbilical cord)
● Considered pluripotent and multipotent too ● Not totipotent, but multipotent

Perinatal stem cells (umbilical cord) (MULTIPOTENT) Adult stem cells (MULTIPOTENT) eg. muscle cell, red blood cell, brain cell
● Can be collected from cord blood at birth ● Undifferentiated cells found in ‘adult’ tissues throughout the body
● Contains multipotent stem cells that can differentiate into ● Give rise to only a few related types of specialised cells for the specific tissue or
some types of cells of the body (limited) organ in which they live
● Not pluripotent or totipotent ● Primary role is to maintain and repair/replace tissue
● Either remain as stem cells or develop into a more specialised cell

Where can scientists obtain stem cells?

- From an embryo, from umbilical cord blood of fetus, from tissues in the body, from bone marrow

Compare between a cancer cell and a stem cell.

- Both cells divide continuously
- Both are somatic cells
- Both are unspecialised cells
- Both bypass apoptosis (programmed cell death)
Diff:
- A cancer cell bypasses cell cycle controls, while a stem cell replicates under normal cell cycle controls.
- Cancer cells divide in an uncontrolled manner, while stem cells divide in a controlled manner.
- Stem cells undergo differentiation, while cancer cells do not differentiate.
- Cancer cells have mutation(s) in the DNA, while stem cells do not have mutation(s) in the DNA

The main difference between replication and duplication of DNA is that replication is the synthesis of an exact replica of DNA while duplication
is the doubling of the amount of DNA as a result of replication.
True: DNA replicates during interphase.
False: DNA duplicates during interphase. “the amount of DNA” is duplicated during interphase.

Which best describes homologous chromosomes?

A. Two chromatids joined together to form on chromosome – Sister chromatids
B. Two chromatids with identical alleles – Sister chromatids/ homozygous
C. Two chromosomes that form a pair at the start of meiosis
D. Two chromosomes with identical alleles – homozygous
E. They contain identical DNA – Sister chromatids
F. They contain the same genes in the same position – but may have different alleles!
G. They have identical alleles – homozygous
H. They replicate during meiosis only – replicates during DNA replication