Ronnee Yashon

Michael Cummings

Chapter 8

DNA Structure
&
DNA Replication
 Lecture Objectives
•To understand the structure and function of DNA

•To understand the structural and functional differences

between DNA and RNA

•To describe Watson and Crick’s three--dimensional model of

DNA
 What is DNA?
It's a history book - a narrative of the journey of our species
through time.
It's a shop manual, with an incredibly detailed blueprint for
building every human cell.
And it's a transformative textbook of medicine, with insights
that will give health care providers immense new powers to
treat, prevent and cure disease."
- Francis Collins
Evidence DNA Carries Genetic
Information

 Chromosomes carries genetic information

 Chromosomes/genes passed from generation to

generation

 Chromosomes components:
◦ Proteins
+
◦ DNA
 How much DNA is in one
cell?
Genome = 46 chromosomes
Genome = approx. 3 billion
base pairs
One base pair is 0.00000000034 meters

DNA sequence in any two people is

99.9% identical – only 0.1% is unique!
A History of DNA
 F. Griffiths (1928)

Tried to determine what

genetic material was made of.
 Griffiths’ Experiment
Cells transformed, hereditary information passed from dead S cells into R cell
Avery, MacCleod & McCarthy (1944)
Tried purifying the transforming
principle to change R-type
Pneumococcus to S-type
Purified DNA, RNA, and protein from
heat-killed S cells

Only DNA able to cause transformation

Co-injected them with the avirulent strain:
When co-injected with protein fraction, the mice lived
with the DNA fraction, the mice died

DNA carrier of genetic information

Result was IGNORED
Most scientists believed protein was the genetic
material.
 The Hershey-Chase Experiment
• Hershey & Chase – 1952
• Performed the definitive
experiment that showed
that DNA was the genetic
material.
• Erwin Chargaff – 1950
Chargaff’s rule
– discovered the % content of the 4 nucleotides was the same in all tissues
of the same species
– percentages could vary from species to species.

• He also found that in all animals (Chargaff’s rule): %G

= %C
%A = %T
Watson and Crick shared the 1962 Nobel Prize for Physiology
and Medicine with Maurice Wilkins. Rosalind Franklin died
before this date.

The Double Helix Model: X-ray diffraction studies

Watson & Crick & helical structure of DNA
Rosalind Franklin
 Organization of DNA Molecules

 Watson and Crick used information from X-ray

diffraction images produced by Rosalind Franklin
 James Watson and Francis Crick
 Model for DNA structure proposed in 1953

X-ray crystallographic data obtained by Rosalind Franklin, combined

with the previous results from Chargaff and others, were fitted
together by Watson and Crick into the double helix model.
 The Double Helix: Watson &
Crick
• James Watson and Francis Crick – 1953

• Presented a model of the structure of DNA.

• It was already known from chemical studies that DNA

was a polymer of nucleotide (sugar, base and
phosphate) units.
 Features of DNA
 Two chains of nucleotides with sugar phosphate backbone

 Double helix, ladder-like molecule with bases on

the inside A pairs with T, and G pairs with C

 Predictive base pairing makes two chains are

Complementary in base composition

Anti-parallel strands: the different

strands in the helix run in opposite (anti-parallel) directions.

Nucleotide Chains in DNA

 The two
polynucleotide
chains in DNA run
in opposite
directions
 The Watson- Crick Model of
DNA

The two polynucleotide chains

are coiled to form a double helix Base pairing is highly specific
 DNA Model
Polynucleotides
have different
chemical groups
at each end:
a phosphate
group at one
end 5’,

And an OH
group attached
to the sugar
molecule 3’ end
of the chain.
 The structure of DNA:
Complementary base pairing
• Each strand of DNA is held together by base pairing
(hydrogen bonding) between the bases of each
strand.
– The complementary base pairing rule:
• A always pairs with T
• C always pairs with G
 Components of Nucleotides
 Three components:
o Nitrogen-containing base
 Purines: adenine and guanine
 Pyrimidines: cytosine, thymine, and uracil
o Sugar
 Ribose or Deoxyribose
o Phosphate group

 Form chains
 The structure of DNA:
Nucleotides
• Nucleotides have one of four bases:
– Adenine (A)
– Thymine (T)
– Guanine (G)
– Cytosine (C)
The structure of DNA: A double
helix
phosphate

• The sugars and

sugar
phosphates form
the outside
“backbone” of the
helix.
• The bases form the
internal “rungs,” like
steps on a twisting
Complementary ladder.
base pairing
 Three Properties of Watson-
Crick Model
 Genetic information stored in sequence of bases in
DNA:
Four bases allows for a high coding capacity

 Offers a molecular explanation for mutation

 Complementary sequence of bases in two

strands of DNA, explains how DNA copies
itself
• DNA stands for deoxyribonucleic acid.
• DNA is common to all living organisms.
DNA is found in the nucleus of eukaryotic cells
 Nucleosome= DNA+proteins Nucleosome=
Protein cluster (histone core) DNA+Histones

Threads of DNA that connect nucleosomes

Each chromosome contains long DNA

molecule, coiled and combined with
proteins

Folded and compacted by a factor of

~10,000

DNA is wound around outside

of a protein cluster to form
nucleosomes

Folding of DNA Chromosomes

DNA Organization in a Chromosome

• DNA in all 46 human chromosomes,

~6 ft
(1.8 m)

• Folded and compacted by a factor of

~10,000

•The genome can fit inside a nucleus

due to extensive coiling
Genetic Information on DNA:
Encoded in sequence of base pairs in a DNA molecule

Each DNA sequence that contains instructions to make

a protein is known as a gene

• Gene
– Consists of hundreds or thousands of nucleotides
– Has a beginning and end
– Chromosome contains thousands of genes
– Mutation: Change in any base pair in a gene
 Genetic Information on DNA
• If DNA were a dictionary, genes would correspond to word entries
in the DNA.
– Meaning of the word is determined by the alphabet sequence.

• If DNA were a playlist in your MP3 player, genes would correspond

to songs in the playlist.
– Tune of the song is determined by the note sequence.
• Meaning of the gene is determined by DNA sequence.
 DNA and RNA
 Organisms contain two types of nucleic acids
 Deoxyribonucleic acid (DNA)
 Ribonucleic acid (RNA)
 DNA in nucleus, RNA in nucleus and cytoplasm

Chemical Subunits of DNA and RNA

 Made up of nucleotides subunits
RNA
RNA Molecules Organization
 Found in nucleus and cytoplasm

 Transfers genetic information from nucleus to

cytoplasm

 Participates in formation of proteins

 Component of ribosomes

 In most cells, single-stranded

DNA vs RNA

DNA and RNA are long linear polymers,

called nucleic acids, that carry
information in a form that can be passed
from one generation to the next
 DNA/RNA differences
RNA is single
stranded.

C C
RNA is much smaller than
G G DNA. RNA contains
information for one gene.
A A DNA contains information
for thousands of genes.
T U

RNA contains U (uracil)

instead of T (thymine)
DNA RNA
The complementary RNA forms from a DNA
template according to the rules of base pairing,
except that in RNA, adenine (A) pairs with uracil
(U).
Two Main Functions of DNA
1. To replicate itself

2. To encode for proteins and RNA molecules

necessary for life in cell or organism
`It has not escaped our notice that the specific
pairing we have postulated immediately
suggests a possible copying mechanism for the
genetic material’

Watson & Crick

Nature (1953)

Original drawing by Francis Crick

 How Is DNA Replicated?
 Before mitosis begins, all cells copy their DNA

 Each daughter cell receives a complete

set of chromosomes

 Occurs in all living things, from

bacteria to humans

 DNA molecule unwinds, each strand

serves as a template for new,
complementary strand

•During DNA replication, the hydrogen bonds

that hold base pairs together are broken and the helix
is unwound.

•Occurs during S phase of the cell cycle

 Steps in Replication
 DNA molecule unwinds

 DNA polymerase
o Reads sequence of template strand
o Links together nucleotides to form
complementary strand that attaches to
old strand

 Each DNA molecule: one old strand and

one new strand
DNA replication
– Complementary sequence of the two strands
explains how DNA can be replicated
 Addition of Nucleotides During
DNA Replication
As the strands uncoil, bases are added to
the newly synthesized strand by
complementary base pairing with bases
in the template strand. The new bases
are linked together by DNA polymerase.
 DNA replication is semi-
conservative

At the end of DNA

replication, two copies of the
original DNA molecule exist.
– Each molecule consists of
an original and a new
strand.
 DNA replication

Sister chromatids

• Chromosomes replicate during the DNA synthesis phase of

interphase.
• The replicated DNA molecules are called sister
chromatids.
• Sister chromatids are joined together at the centromere.
 Chromatids Are Formed in Replication

• When replication is
complete, two
chromatids joined at
a common
centromere

• Centromeres divide
during mitosis, each
chromatid becomes
a chromosome
 Take home message
DNA is the blueprint of life
Q1.

Where two alternatives for a trait are tall and

short, and tall is dominant, the genotype of a
heterozygous individual would be expressed
a. ss
b. SS
c. Ss
d. tall
Q2.

Individuals with complete androgen insensitivity

A) menstruate after reaching puberty.
B) often have testes present in their abdomens.
C) usually have no problems reproducing.
D) have a set of XX sex chromosomes.
 Q3.

Concordance of a trait helps establish whether

or not a trait
A) is associated with genetic disease.
B) is recessive.
C) is autosomal.
D) is sex-linked.
E) has a genetic basis
 Q4.

A dominant allele is
a. an allele that expresses its phenotypic effect
even when it is present with a recessive allele.
b. an allele whose presence can be hidden.
c. only present in males.
d. only present in females.
e. always present in homozygous individuals.
 Study the pedigrees of family A and family B in the figure below.

I B
I A

II

III

i)Which family pedigree shows an autosomal dominant mode of inheritance?

(ii) Give reasons for your choice.
(i) What type of inheritance is demonstrated by the other family?
(ii) If individual III-1 (in the non-autosomal dominant pedigree) marries a male
heterozygous for the trait, what is the chance that their first child will show the trait?