The Molecular Basis of Inheritance

C
A

T
T

1 nm
C

G
C
A
C

3.4 nm

G
T

A
T

A
A

T
T

G
A

Figure 16.7a, c

0.34 nm

(a) Key features of DNA structure

(c) Space-filling model

1962: Nobel Prize in Physiology and Medicine

Watson, J.D. and F.H. Crick, Molecular Structure of
Nucleic Acids: A Structure for Deoxynucleic Acids. Nature
171 (1953), p. 738.

James D.
Watson

Francis H.
Crick

Maurice H. F.
Wilkins
What about?
Rosalind Franklin

The Structure of DNA

DNA is composed of four nucleotides,

each containing: adenine, cytosine,
thymine, or guanine.

The amounts of A = T, G = C, and

purines = pyrimidines [Chargaffs
Rule].

DNA is a double-stranded helix with

antiparallel strands [Watson and Crick].

Nucleotides in each strand are linked

by 5-3 phosphodiester bonds

Bases on opposite strands are linked

by hydrogen bonding: A with T, and G
with C.

The Basic Principle: Base Pairing to a

Template Strand
The relationship between structure and
function is manifest in the double helix
Since the two strands of DNA are
complementary each strand acts as a
template for building a new strand in
replication

DNA replication
The parent molecule unwinds, and two new
daughter strands are built based on basepairing rules
T

A
G

(a) The parent molecule has two

complementary strands of DNA.
Each base is paired by hydrogen
bonding with its specific partner,
A with T and G with C.

(b) The first step in replication is

separation of the two DNA
strands.

(c) Each parental strand now

serves as a template that
determines the order of
nucleotides along a new,
complementary strand.

(d) The nucleotides are connected

to form the sugar-phosphate
backbones of the new strands.
Each daughter DNA
molecule consists of one parental
strand and one new strand.

DNA Replication is Semi-conservative

Each 2-stranded
daughter molecule is
only half new
One original strand was
used as a template to
make the new strand

DNA Replication
The copying of DNA is remarkable in its speed and accuracy
Involves unwinding the double helix and synthesizing two
new strands.
More than a dozen enzymes and other proteins participate
in DNA replication
The replication of a DNA molecule begins at special sites
called origins of replication, where the two strands are
separated

Origins of Replication
A eukaryotic chromosome may have hundreds or
even thousands of replication origins
Origin of replication

1 Replication begins at specific sites

where the two parental strands
separate and form replication
bubbles.

Parental (template) strand

Daughter (new) strand

Bubble

0.25 m

Replication fork

2 The bubbles expand laterally, as

DNA replication proceeds in both
directions.
3 Eventually, the replication
bubbles fuse, and synthesis of
the daughter strands is
complete.

Two daughter DNA molecules

(a) In eukaryotes, DNA replication begins at many sites along the giant
DNA molecule of each chromosome.

(b) In this micrograph, three replication

bubbles are visible along the DNA of
a cultured Chinese hamster cell (TEM).

Mechanism of DNA Replication

DNA replication is catalyzed by DNA polymerase which needs an RNA primer
RNA primase synthesizes primer on DNA strand
DNA polymerase adds nucleotides to the 3 end of the growing strand

Mechanism of DNA Replication

Nucleotides are added by complementary base pairing with the

template strand
The substrates, deoxyribonucleoside triphosphates, are
hydrolyzed as added, releasing energy for DNA synthesis.

The Mechanism of DNA Replication

DNA synthesis on the leading strand is continuous

The lagging strand grows the same general direction as the leading
strand (in the same direction as the Replication Fork). However,
DNA is made in the 5-to-3 direction
Therefore, DNA synthesis on the lagging strand is discontinuous
DNA is added as short fragments (Okasaki fragments) that are
subsequently ligated together

DNA polymerase I degrades the

RNA primer and replaces it with
DNA

The Mechanism of DNA Replication

Many proteins assist in DNA replication

DNA helicases unwind the double helix, the

template strands are stabilized by other
proteins

Single-stranded DNA binding proteins make

the template available

RNA primase catalyzes the synthesis of short

RNA primers, to which nucleotides are added.

DNA polymerase III extends the strand in the

5-to-3 direction

DNA polymerase I degrades the RNA primer

and replaces it with DNA

DNA ligase joins the DNA fragments into a

continuous daughter strand

Enzymes in DNA replication

Helicase unwinds
parental double helix

DNA polymerase III

binds nucleotides
to form new strands

Binding proteins
stabilize separate
strands

Primase adds
short primer
to template strand

DNA polymerase I
(Exonuclease) removes
RNA primer and inserts
the correct bases

Ligase joins Okazaki

fragments and seals
other nicks in sugarphosphate backbone

Replication
3
3

5
3
5

Helicase protein binds to DNA sequences called

origins and unwinds DNA strands.
Binding proteins prevent single strands from rewinding.
Primase protein makes a short segment of RNA
complementary to the DNA, a primer.

Replication
Overall direction
of replication

3
3

5
3
5

3
5

DNA polymerase enzyme adds DNA nucleotides

to the RNA primer.

Replication
Overall direction
of replication

3
5

5
3
5

3
5

DNA polymerase enzyme adds DNA nucleotides

to the RNA primer.
DNA polymerase proofreads bases added and
replaces incorrect nucleotides.

Replication
Overall direction
of replication

3
3

5
3
5

Leading strand synthesis continues in a

5 to 3 direction.

3
5

Replication
Overall direction
of replication

3
3

Okazaki fragment

3
5

3 5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

3
5

Replication
Overall direction
of replication

3
3

5
Okazaki fragment

3
5

3 5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

3
5

Replication
3
5

3
5
3
5

3 5

35

3
5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

Replication
3
5

3
5
3
5

35

35

3
5

Leading strand synthesis continues in a

5 to 3 direction.
Discontinuous synthesis produces 5 to 3 DNA
segments called Okazaki fragments.

Replication
3
5

3
5
3
5

35

35

3
5

Exonuclease activity of DNA polymerase I

removes RNA primers.

Replication
3
3
5
3
5

35

3
5

Polymerase activity of DNA polymerase I fills the gaps.

Ligase forms bonds between sugar-phosphate backbone.

Replication Fork Overview

Proofreading
DNA must be faithfully replicatedbut
mistakes occur
DNA polymerase (DNA pol) inserts the wrong
nucleotide base in 1/10,000 bases
DNA pol has a proofreading capability and can correct
errors

Mismatch repair: wrong inserted base can be

removed
Excision repair: DNA may be damaged by
chemicals, radiation, etc. Mechanism to cut out
and replace with correct bases

Mutations
A mismatching of base pairs, can occur at a
rate of 1 per 10,000 bases.
DNA polymerase proofreads and repairs
accidental mismatched pairs.
Chances of a mutation occurring at any one
gene is over 1 in 100,000
Because the human genome is so large,
even at this rate, mutations add up. Each of
us probably inherited 3-4 mutations!

Proofreading and Repairing DNA

DNA polymerases
proofread newly made
DNA, replacing any
incorrect nucleotides
In mismatch repair of DNA,
repair enzymes correct
errors in base pairing
In nucleotide excision DNA
repair nucleases cut out
and replace damaged
stretches of DNA

1 A thymine dimer
distorts the DNA molecule.
2 A nuclease enzyme cuts
the damaged DNA strand
at two points and the
damaged section is
removed.
Nuclease

DNA
polymerase

3 Repair synthesis by
a DNA polymerase
fills in the missing
nucleotides.
DNA
ligase

4 DNA ligase seals the

Free end of the new DNA
To the old DNA, making the
strand complete.

Accuracy of DNA Replication

The chromosome of E. coli bacteria contains
about 5 million bases pairs
Capable of copying this DNA in less than an hour

The 46 chromosomes of a human cell contain

about 6 BILLION base pairs of DNA!!
Printed one letter (A,C,T,G) at a timewould fill up
over 900 volumes of Campbell.
Takes a cell a few hours to copy this DNA
With amazing accuracy an average of 1 per
billion nucleotides

Protein Synthesis
The information content of DNA is in the form of
specific sequences of nucleotides along the DNA
strands
The DNA inherited by an organism leads to specific
traits by dictating the synthesis of proteins
The process by which DNA directs protein synthesis,
gene expression includes two stages, called
transcription and translation

Transcription and Translation

Cells are governed by a cellular chain of command
DNA RNA protein

Transcription

Is the synthesis of RNA under the direction of DNA

Produces messenger RNA (mRNA)

Translation
Is the actual synthesis of a polypeptide, which occurs under
the direction of mRNA
Occurs on ribosomes

Transcription and Translation

In a eukaryotic cell the nuclear envelope separates transcription

from translation
Extensive RNA processing occurs in the nucleus

Nuclear
envelope

DNA

TRANSCRIPTION

Pre-mRNA

RNA PROCESSING

mRNA

Ribosome
TRANSLATION
Polypeptide

(b) Eukaryotic cell. The nucleus provides a separate

compartment for transcription. The original RNA
transcript, called pre-mRNA, is processed in various
ways before leaving the nucleus as mRNA.

Transcription
Transcription is the DNAdirected synthesis of RNA
RNA synthesis
Is catalyzed by RNA polymerase,
which pries the DNA strands
apart and hooks together the
RNA nucleotides
Follows the same base-pairing
rules as DNA, except that in
RNA, uracil substitutes for
thymine

RNA

RNA is single stranded, not double stranded like DNA

RNA is short, only 1 gene long, where DNA is very long and contains
many genes
RNA uses the sugar ribose instead of deoxyribose in DNA
RNA uses the base uracil (U) instead of thymine (T) in DNA.

Table 17.1

Synthesis of an RNA Transcript

The stages of
transcription are
Initiation
Elongation
Termination

Promoter

Transcription unit

5
3

3
5

Start point
RNA polymerase

DNA
Initiation. After RNA polymerase binds to
the promoter, the DNA strands unwind, and
the polymerase initiates RNA synthesis at the
start point on the template strand.

5
3

Unwound
DNA

3
5

Template strand of
DNA
transcript
2 Elongation. The polymerase moves downstream, unwinding the
DNA and elongating the RNA transcript 5 3 . In the wake of
transcription, the DNA strands re-form a double helix.
Rewound
RNA

RNA
5
3

3
5

3
5

RNA
transcript

3 Termination. Eventually, the RNA

transcript is released, and the
polymerase detaches from the DNA.

5
3

3
5
5

Completed RNA
transcript

Synthesis of an RNA Transcript - Initiation

Promoters signal the initiation

of RNA synthesis
Transcription factors help
eukaryotic RNA polymerase
recognize promoter sequences

1 Eukaryotic promoters

TRANSCRIPTION

DNA

RNA PROCESSING

Pre-mRNA

mRNA
TRANSLATION

Ribosome
Polypeptide

5
3

Promoter

3
5

T A T A A AA
AT A T T T T

TATA box

Start point

Template
DNA strand

Several transcription
factors

Transcription
factors

5
3

3 Additional transcription

3
5

factors

RNA polymerase II

5
3

Transcription factors

3
5

5
RNA transcript
Transcription initiation complex

Synthesis of an RNA Transcript - Elongation

RNA polymerase synthesizes a single strand of RNA against the DNA template strand (antisense strand), adding nucleotides to the 3 end of the RNA chain

As RNA polymerase moves along the DNA it continues to untwist the double helix, exposing
about 10 to 20 DNA bases at a time for pairing with RNA nucleotides

Non-template
strand of DNA

Elongation

RNA nucleotides

RNA
polymerase

A T

3 end

U
C A

Newly made
RNA

Direction of transcription
(downstream)

Template
strand of DNA

Synthesis of an RNA Transcript - Termination

Specific sequences in the DNA signal termination

of transcription
When one of these is encountered by the
polymerase, the RNA transcript is released from
the DNA and the double helix can zip up again.

Transcription Overview

Post Termination RNA Processing

Most eukaryotic mRNAs arent ready to be translated into protein directly after being
transcribed from DNA. mRNA requires processing.

Transcription of RNA processing occur in the nucleus. After this, the messenger RNA moves to
the cytoplasm for translation.

The cell adds a protective cap to one end, and a tail of As to the other end. These both
function to protect the RNA from enzymes that would degrade

Most of the genome consists of non-coding regions called introns

Non-coding regions may have specific chromosomal functions or have regulatory purposes

Introns also allow for alternative RNA splicing

Thus, an RNA copy of a gene is converted into messenger RNA by doing 2 things:

Add protective bases to the ends

Cut out the introns

Alteration of mRNA Ends

Each end of a pre-mRNA molecule is modified in a
particular way
The 5 end receives a modified nucleotide cap
The 3 end gets a poly-A tail

A modified guanine nucleotide

added to the 5 end
TRANSCRIPTION

RNA PROCESSING

50 to 250 adenine nucleotides

added to the 3 end

DNA

Pre-mRNA

mRNA

Protein-coding segment

Polyadenylation signal
3

G P P P

AAUAAA

AAAAAA

Ribosome
TRANSLATION

5 Cap
Polypeptide

5 UTR

Start codon Stop codon

3 UTR

Poly-A tail

RNA Processing - Splicing

The original transcript from

the DNA is called pre-mRNA.

It contains transcripts of both

introns and exons.

The introns are removed by a

process called splicing to
produce messenger RNA
(mRNA)

RNA Processing
Proteins often have a modular architecture consisting
of discrete structural and functional regions called
domains
In many cases different exons code for the different
domains in a protein
DNA

Gene
Exon 1

Exon 2

Intron

Intron

Exon 3

Transcription
RNA processing
Translation
Domain 3
Domain 2
Domain 1

Figure 17.12

Polypeptide

Translation
Translation is the RNA-directed
synthesis of a polypeptide
Translation involves

TRANSCRIPTION

DNA
mRNA
Ribosome

TRANSLATION
Polypeptide

mRNA
Ribosomes - Ribosomal RNA
Transfer RNA
Genetic coding - codons

Amino
acids

Polypeptide

Trp

tRNA with
amino acid
Ribosome attached

Phe

Gly
tRNA

GC

A A A
U G G U U U G G C

Codons

5
mRNA

Anticodon

The Genetic Code

Genetic information is encoded as a sequence of nonoverlapping base

triplets, or codons

Gene 2

DNA
molecule

Gene 1
Gene 3

DNA strand
(template)

A C C A A A C C G A G

TRANSCRIPTION

mRNA

U G G U U U G G C U C A
Codon

TRANSLATION

Protein

Trp
Amino acid

Phe

Gly

Ser

The Genetic Code

Codons: 3 base code for the production of a specific amino acid,

sequence of three of the four different nucleotides

Since there are 4 bases and 3 positions in each codon, there are 4 x 4 x
4 = 64 possible codons

64 codons but only 20 amino acids, therefore most have more than 1
codon

3 of the 64 codons are used as STOP signals; they are found at the end
of every gene and mark the end of the protein

One codon is used as a START signal: it is at the start of every protein

Universal: in all living organisms

The Genetic Code

Second mRNA base

U
C
A
UAU
UUU
UCU
Tyr
Phe
UAC
UUC
UCC
U
UUA
UCA Ser UAA Stop
UAG Stop
UUG Leu UCG
CUU
CUC
C
CUA
CUG

CCU
CCC
Leu CCA
CCG

Pro

AUU
AUC
A
AUA
AUG

ACU
ACC
ACA
ACG

Thr

GUU
G GUC
GUA
GUG

lle
Met or
start

GCU
GCC
Val
GCA
GCG

Ala

U
UGU
Cys
UGC
C
UGA Stop A
UGG Trp G
U
CAU
CGU
His
CAC
CGC
C
Arg
CAA
CGA
A
Gln
CAG
CGG
G
U
AAU
AGU
Asn
AAC
AGC Ser C
A
AAA
AGA
Lys
AAG
AGG Arg G
U
GAU
GGU
Asp
C
GAC
GGC
Gly
GAA
GGA
A
Glu
GAG
GGG
G

Third mRNA base (3 end)

First mRNA base (5 end)

A codon in messenger RNA is either translated into an amino acid

or serves as a translational start/stop signal

Transfer RNA

Consists of a single RNA strand that is only about 80 nucleotides long

Each carries a specific amino acid on one end and has an anticodon on
the other end
A special group of enzymes pairs up the proper tRNA molecules with
their corresponding amino acids.
tRNA brings the amino acids to the ribosomes,

A
C
C
A 5
C G
The anticodon is the 3 RNA bases that
G C
C G
matches the 3 bases of the codon on the
U G
U A
mRNA molecule
A U
A U
U C
UA
C A C AG
*
G
*
G U G U *
C
C
* *
U C
*
* G AG C
(a) Two-dimensional structure. The four base-paired regions and three
G C
U A
loops are characteristic of all tRNAs, as is the base sequence of the
* G
amino acid attachment site at the 3 end. The anticodon triplet is
A
A*
C
unique to each tRNA type. (The asterisks mark bases that have been
U
*
chemically modified, a characteristic of tRNA.)
A
G
A

Amino acid
attachment site

Anticodon

C U C
G A G

A G *
*
G
A G G

Hydrogen
bonds

Transfer RNA

3 dimensional tRNA molecule is roughly L shaped

5
3

Amino acid
attachment site

Hydrogen
bonds

A AG
3
Anticodon
(b) Three-dimensional structure

Anticodon

(c) Symbol used

in the book

Ribosomes

Ribosomes facilitate the specific coupling of tRNA anticodons with

mRNA codons during protein synthesis
The 2 ribosomal subunits are constructed of proteins and RNA
molecules named ribosomal RNA or rRNA

DNA

TRANSCRIPTION

mRNA
Ribosome
TRANSLATION

Polypeptide

Growing
polypeptide

Exit tunnel

tRNA
molecules
E

Large
subunit
P A
Small
subunit

5
mRNA

(a) Computer model of functioning ribosome. This is a model of a bacterial

ribosome, showing its overall shape. The eukaryotic ribosome is roughly
similar. A ribosomal subunit is an aggregate of ribosomal RNA molecules
and proteins.

Building a Polypeptide
Amino end

Growing polypeptide

Next amino acid

to be added to
polypeptide chain

tRNA
3

mRNA

Codons

(c) Schematic model with mRNA and tRNA. A tRNA fits into a binding site when its anticodon basepairs with an mRNA codon. The P site holds the tRNA attached to the growing polypeptide. The A
site holds the tRNA carrying the next amino acid to be added to the polypeptide chain. Discharged
tRNA leaves via the E site.

Building a Polypeptide
We can divide translation into three stages
Initiation
Elongation
Termination

The AUG start codon is recognized by methionyl-tRNA or Met

Once the start codon has been identified, the ribosome
incorporates amino acids into a polypeptide chain
RNA is decoded by tRNA (transfer RNA) molecules, which each
transport specific amino acids to the growing chain
Translation ends when a stop codon (UAA, UAG, UGA) is reached

Initiation of Translation

The initiation stage of translation brings together mRNA, tRNA

bearing the first amino acid of the polypeptide, and two subunits
of a ribosome

t
Me

P site

3 U A C 5
5 A U G 3

Initiator tRNA

t
Me

GTP

GDP

mRNA
5

Start codon

mRNA binding site

Large
ribosomal
subunit

Small
ribosomal
subunit

A small ribosomal subunit binds to a molecule of

mRNA. In a prokaryotic cell, the mRNA binding site
on this subunit recognizes a specific nucleotide
sequence on the mRNA just upstream of the start
codon. An initiator tRNA, with the anticodon UAC,
base-pairs with the start codon, AUG. This tRNA
carries the amino acid methionine (Met).

A
3

Translation initiation complex

The arrival of a large ribosomal subunit completes

the initiation complex. Proteins called initiation
factors (not shown) are required to bring all the
translation components together. GTP provides
the energy for the assembly. The initiator tRNA is
in the P site; the A site is available to the tRNA
bearing the next amino acid.

Elongation of the Polypeptide Chain

In the elongation stage, amino acids are added one by one to

the preceding amino acid

TRANSCRIPTION

1 Codon recognition. The anticodon

of an incoming aminoacyl tRNA
base-pairs with the complementary
mRNA codon in the A site. Hydrolysis
of GTP increases the accuracy and
efficiency of this step.

Amino end
of polypeptide

DNA
mRNA
Ribosome

TRANSLATION

Polypeptide

mRNA
Ribosome ready for
next aminoacyl tRNA

E
3
P A
site site

2 GTP
2 GDP

E
P

3 Translocation. The ribosome

translocates the tRNA in the A
site to the P site. The empty tRNA
in the P site is moved to the E site,
where it is released. The mRNA
moves along with its bound tRNAs,
bringing the next codon to be
translated into the A site.

GDP
GTP

E
P

A
2 Peptide bond formation. An
rRNA molecule of the large
subunit catalyzes the formation
of a peptide bond between the
new amino acid in the A site and
the carboxyl end of the growing
polypeptide in the P site. This step
attaches the polypeptide to the
tRNA in the A site.

Termination of Translation

The final stage is termination when the ribosome reaches a stop codon
in the mRNA

Release
factor

Free
polypeptide
5
3

3
5

Stop codon
(UAG, UAA, or UGA)
1 When a ribosome reaches a stop 2 The release factor hydrolyzes 3 The two ribosomal subunits
codon on mRNA, the A site of the
the bond between the tRNA in and the other components of
ribosome accepts a protein called the P site and the last amino
the assembly dissociate.
a release factor instead of tRNA.
acid of the polypeptide chain.
The polypeptide is thus freed
from the ribosome.

Translation
The final step in translation is termination. When the
ribosome reaches a STOP codon, there is no
corresponding transfer RNA.
Instead, a small protein called a release factor
attaches to the stop codon.
The release factor causes the whole complex to fall
apart: messenger RNA, the two ribosome subunits,
the new polypeptide.
The messenger RNA can be translated many times,
to produce many protein copies.

A summary of transcription and translation in a eukaryotic cell

DNA

TRANSCRIPTION
1RNA is transcribed

from a DNA template.

3

RNA
transcript

A
lyPo

RNA
polymerase
Exon

RNA PROCESSING
2

In eukaryotes, the
RNA transcript (premRNA) is spliced and
modified to produce
mRNA, which moves
from the nucleus to the
cytoplasm.

RNA transcript
(pre-mRNA)
Intron

NUCLEUS

Amino
acid

FORMATION OF
INITIATION COMPLEX

CYTOPLASM

Aminoacyl-tRNA
synthetase

p
Ca

AMINO ACID ACTIVATION

tRNA

3 After leaving the

Each amino acid

attaches to its proper tRNA
with the help of a specific
enzyme and ATP.

nucleus, mRNA attaches

to the ribosome.
Growing
polypeptide

mRNA
lyPo

Activated
amino acid
A
lyPo

Ribosomal
subunits

p
Ca

5
TRANSLATION

C
A C

AC

A A A
U G G U U U A U G

Figure 17.26

Codon
Ribosome

Anticodon

A succession of tRNAs
add their amino acids to
the polypeptide chain
as the mRNA is moved
through the ribosome
one codon at a time.
(When completed, the
polypeptide is released
from the ribosome.)

Post-translation
The new polypeptide is now floating loose in the
cytoplasm if translated by a free ribosme.
It might also be inserted into a membrane, if
translated by a ribosome bound to the endoplasmic
reticulum.
Polypeptides fold spontaneously into their active
configuration, and they spontaneously join with other
polypeptides to form the final proteins.
Sometimes other molecules are also attached to the
polypeptides: sugars, lipids, phosphates, etc. All of
these have special purposes for protein function.

Mutation Causes and Rate

The natural replication of DNA produces occasional
errors. DNA polymerase has an editing mechanism
that decreases the rate, but it still exists.\
Typically genes incur base substitutions about once
in every 10,000 to 1,000,000 cells.
Since we have about 6 billion bases of DNA in each
cell, virtually every cell in your body contains several
mutations.
However, most mutations are neutral: have no effect.
Only mutations in cells that become sperm or eggs
are passed on to future generations.
Mutations in other body cells only cause trouble when
they cause cancer or related diseases.

Point mutations
Point mutations involve alterations in the structure or
location of a single gene. Generally, only one or a few
base pairs are involved.
Point mutations can signficantly affect protein
structure and function
Point mutations may be caused by physical damage
to the DNA from radiation or chemicals, or may occur
spontaneously
Point mutations are often caused by mutagens

Mutagens

Mutagens are chemical or physical agents that interact with DNA to

cause mutations.
Physical agents include high-energy radiation like X-rays and
ultraviolet light
Chemical mutagens fall into several categories.

Chemicals that are base analogues that may be substituted into DNA, but
they pair incorrectly during DNA replication.
Interference with DNA replication by inserting into DNA and distorting the
double helix.
Chemical changes in bases that change their pairing properties.

Tests are often used as a preliminary screen of chemicals to identify

those that may cause cancer
Most carcinogens are mutagenic and most mutagens are carcinogenic.

Viral Mutagens
Scientists have recognized a number of tumor
viruses that cause cancer in various animals,
including humans
About 15% of human cancers are caused by viral
infections that disrupt normal control of cell
division
All tumor viruses transform cells into cancer cells
through the integration of viral nucleic acid into
host cell DNA.

Point Mutation
The change of a single nucleotide in the DNAs
template strand leads to the production of an
abnormal protein
Wild-type hemoglobin DNA
3

Mutant hemoglobin DNA

5

C T

In the DNA, the

mutant template
strand has an A where
the wild-type template
has a T.

G U A

The mutant mRNA has

a U instead of an A in
one codon.

C A

mRNA

mRNA
G A

Normal hemoglobin

Sickle-cell hemoglobin

Glu

Val

The mutant (sickle-cell)

hemoglobin has a valine
(Val) instead of a glutamic
acid (Glu).

Types of Point Mutations

Point mutations within a gene can be divided into
two general categories
Base-pair substitutions
Base-pair insertions or deletions

Substitutions

A base-pair substitution is the replacement of one nucleotide and its

partner with another pair of nucleotides

Silent - changes a codon but codes for the same amino acid
Missense - substitutions that change a codon for one amino acid into a codon for a
different amino acid
Nonsense -substitutions that change a codon for one amino acid into a stop codon
Wild type
mRNA
Protein

A U G
Met

A A G U U U G G C U A A
Lys

Phe

Gly

3
Stop

Amino end

Carboxyl end
Base-pair substitution
No effect on amino acid sequence
U instead of C
A U G A A G U U U G G U U A A
Met

Lys

Missense

Phe

Gly

Stop

A instead of G

A U G A A G U U U A G U U A A
Met
Nonsense

Lys

Phe

Ser

Stop

U instead of A

A U G U A G U U U G G C U A A
Met

Stop

Insertions and Deletions

Insertions and deletions

Are additions or losses of nucleotide pairs in a gene

May produce frameshift mutations that will change the reading
frame of the gene, and alter all codons downstream from the
mutation.
Wild type
mRNA
Protein

A UG A A GU U U G G C U A A
Met

Lys

Gly

Phe

Stop

Amino end
Carboxyl end
Base-pair insertion or deletion
Frameshift causing immediate nonsense

Extra U
AU G U A AG U U U G GC U A
Met

Stop

Frameshift causing
extensive missense

U Missing

A U G A A GU U G G C U A A
Met

Lys

Leu

Ala

Insertion or deletion of 3 nucleotides:

no frameshift but extra or missing amino acid

A AG

Missing

A U G U U U G G C U A A
Met

Phe

Gly

Stop