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8.5 DNA Repair
At the end of S phase, DNA polymerase has
copied both strands of template DNA
DNA polymerase does make mistakes
-1 mistake every 10,000 bases
What is a mutation?
• Mutation
– any change in DNA sequence
• Results vary
– Silent (very minor)
– Harmful (major)
– Lethal (death)
• These mutations will be passed on to next
generation of cells
DNA Repair Mechanisms
• Body must fix errors(mutations) in DNA
• Two types
– 1. DNA polymerases proofreading
• Most common way of repair
– 2. Excision Repair
Polymerase Proofreading
• DNA polymerase makes a mistake every
10,000 bases
• As DNA polymerase adds nucleotide, it
proofreads
– Will remove wrong nucleotide
– Add correct nucleotide
After it is done, only 1 error every 10 million
bases
2nd method: Excision Repair
• Other mutations arise
– Not during DNA replication
– Other times during cell life
• Caused by outside Mutagenic factors
– Chemical
– radiation
Chemical Mutagenic Factors
• Anything that causes a mutation, a change
or error in DNA sequence
– 1. Chemical Factors
• Chemical molecules physically bind to DNA
– Ex. Benzopyrene
– Hetrocyclic amines
– pesticides
2. Radiation
• Physically damages DNA
Radiation Mutagenic Factors
• Anything that causes a mutation, a change
or error in DNA sequence
2. Radiation: Physically damages DNA
• Ionizing Radiation
– X-rays
 Actually punch holes through DNA
• UV Radiation
– Sunlight
 Causes kink between two thymines
UV Radiation Damage to DNA
• Causes portions of DNA to be bound
together
N
T
T
N
N
A
A
N
UV Radiation Damage to DNA
• Creates “Thymine Dimers”
• Does sunblock prevent mutations?
N
T
T
N
N
A
A
N
Excision Repair
• The mutations
must be detected
and corrected
Excision Repair
• Most common
mutations are
mismatches(wrong
bases paired up)
• Or a chemical
molecule binds
DNA
Excision Repair
• Special enzymes constantly
•
•
circulate
Travel up and down DNA
til they find “damaged
DNA”
Mismatched bases don’t
bond well– form hump
Excision Repair
• 2nd step: Incision
– Enzyme breaks sugarphosphate bonds
between damaged DNA
and normal DNA
• 3rd step: Excision
– Damaged DNA region
is removed
Excision Repair
• 4th step: Re-synthesis
– DNA polymerase fills in
deleted region
• Last step:
– “Ligase” forms bonds
between new region and
rest of DNA strand
DNA Repair
• What would happen if your
•
body couldn’t repair
mutations as efficiently?
What if you couldn’t fix UV
damage?
• Anyone ever watch “The
Others?”
http://www.wwlp.com/news/segments/sybersy/others.jpg
Xeroderma Pigmentosa
• Autosomal recessive disease(very rare)
• Mutation in DNA repair protein
– Protein responsible for replacing nucleotides
in DNA of skin damaged by UV radiation
Cells expose to sunlight have damage to DNA
Now they can’t fix it
Xeroderma Pigmentosa
• Cannot be exposed to sunlight
• Not even strong fluorescent
•
•
light
Must stay indoors with
windows covered to block out
light.
Only a few seconds of
exposure
– Cause 3rd degree burns
– Skin cancer