MUTASI

dan dna repair

• Mutation: A change in the base sequence of
the DNA
• Mutations are changes in the genotype which
may or may not affect the phenotype
 Causes of mutations
• Spontaneous mutations
– Occur in the absence of mutation causing agents
– Due to occasional mistakes in DNA replication
• Induced mutations
– Caused by mutagens, agents such as chemicals
and radiation which induce mutations
 MUTATIONS
• Mutations
– Many inherited diseases result from mutated
genes
– Diseases such as various cancers can be caused by
environmental agents known to
cause DNA mutations
• “Mutagens”

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 Types of mutations

• Base substitutions
– The most common type of mutation
– A single base pair is replaced by another
• Frame shift mutations
– One or more base pairs are inserted or deleted in
the DNA
– Results in a change in the reading of codons
 Chemical mutagens
• Example: Nitrous acid alters adenine such that it pairs
with cytosine instead of thymine
Substitutions, Insertions And
Deletions Are Most Common

Unless it is an
in-frame del/ins, i.e.
multiple of 3
 Radiation
• Ionizing radiation e.g., Xrays and gamma rays
Causes the formation of ions that can react with
nucleotides (causing base changes) and the
deoxyribose-phosphate backbone (causes
chromosomes to break).

• UV radiation
Induces formation of
covalent bonds between
adjacent thymines to form
thymine dimers which can not be replicated
 Single-Nucleotide Substitutions Often Arise
Because Of DNA Polymerase Errors
Transition = purine-purine substitution or pyrimidine-pyrimidine substitution

Transversion = purine-pyrimidine substitution or vice versa

Missense mutation—causes one amino acid to replace another

Nonsense mutation—creates a STOP codon at the site of the mutation

Neutral mutation—changes the amino acid content of the protein, but has no
functional consequences

Silent, aka synonymous, mutation—does not change the amino acid content of the
protein
Intercalating Mutations (e.g. EtBr)
 MUTATIONS
• Two types of base substitutions
– Transition
• Pyrimidine changed to another pyrimidine
– e.g., C  T
• Purine changed to another purine
– e.g., A  G
– Transversion
• Purines and pyrimidines are
interchanged
– e.g., A  C
• More rare than transitions
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 Consequences of base substitutions
• Silent mutation: base change results in no
change of the amino acid sequence of the
translated protein
• Silent mutations have no effect on phenotype
• A result of the fact that multiple codons can
code for the same amino acid
– E.g., AGU and AGC both code for Serine
 Consequences of base substitutions
• Missense mutation: base change results in the
change of an amino acid in the translated protein
 Consequences of missense mutations
• The amino acid substitution induced by the
missense mutation may have no effect on the
function of the protein OR
• It may abolish the activity of the protein or
alter its function having an effect on
phenotype
Example: sickle cell disease in humans is due
to a missense mutation in the gene for globin.
As a result the shape of red blood cells is
altered affecting their movement through
capillaries.
 Consequences of base substitutions
• Nonsense mutation: base change generates a stop
codon in place of that coding for an amino acid
• Results in production of a truncated protein. Usually
results in a non-functional protein
 Consequences of frameshift mutations
• Frameshift mutation: addition or deletion of one or more
bases
• Results in misreading of the codons (changed reading
frame)
• Almost always results in long stretches of altered amino
acids and the production of inactive protein
EFFECTS OF MUTATIONS

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EFFECTS OF MUTATIONS

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 Nucleotide Excision Repair
• In nucleotide excision
repair, a nuclease cuts
out a segment of a
damaged strand.
– The gap is filled in by
DNA polymerase and
ligase.

Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Genetic Disorders Resulting From
Deficiencies In DNA Repair
 Xeroderma Pigmentosum
• Individuals with this
genetic disease have
defective repair
enzymes
– can’t remove thymine
dimers caused by UV
light
– very sensitive to sunlight
and often get skin
cancers
From: Concepts of Genetics, 6th edition,
Klug and Cummings, Prentice Hall

Note the moles on/near the boy’s nose

 What can happen when a mutation occurs in the DNA
(e.g. sickle cell anemia)

Figure 7.1 Concept of a mutation in the protein-coding region of a gene. (Note

that not all mutations lead to altered proteins and that not all mutations are in
protein-coding regions.)
 Translation: Making Proteins
These are the abbreviations for the amino acids A group of three
nucleotides in
messenger RNA
codes for a
certain amino
acid to be placed
in a protein.
Each group of
three
nucleotides is
called a CODON.

http://www2.hawaii.edu/~johnb/micro/micr230/micr230_lectures/lecture9_files/image001.gif
 DNA Repair
• DNA repair mechanisms are placed into
different categories on the basis of the way
they operate
– Direct correction or direct reversal- reversing the
damage
– Excise the damaged areas and then repair the gap
by new DNA synthesis
 DNA Repair
• Spontaneous DNA damage
• Pathways to remove DNA damage
• Damage detection
• The repair of Double-strand break
• DNA repair enzymes
Mutation Generation passed on to daughter
DNAs
Emergency DNA Repair for Double helix break
 DNA REPAIR
• Living cells contain several DNA repair systems
– Able to fix different types of DNA alterations

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