Genetics News

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Genetics News
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Mutation - Overview
Mechanism of mutation Spontaneous Induced
Duplication/Insertions Mechanism (example
lacI) Fragile X syndrome
Repair of mutation Bypass replication Excision
repair Mismatch repair
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Mutation and its Avoidance
Thrust
Parry
DNA damage Base substitution Base
mimicry Intercalation
Reversal of lesion Bypass of lesion General
excision pathway Specific excision
pathway Mismatch repair pathway
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Routes to Mutation
DNA Damage
UV
Pyrimidine dimers T-T C-T T-C
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Repair Strategy 1
Reversal of mutation
Light
DNA photolyase
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Repair Strategy 2
Bypass of mutation
DNA Polymerase III Faithful
Error-correcting
SOS response Induced by DNA damage
Elicits repair enzymes Recruits DNA Pol I
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Repair Strategy 2
Bypass of mutation
SOS-induced genes
Modified DNA Polymerase III Resourceful
Innovative
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Repair Strategy 2
Bypass of mutation
When in doubt, A
Modified DNA Polymerase III Resourceful
Innovative
5'-AGATTGACCTAGAT3'-CCTAACTGGATCTATTGTAA
5'-AGATTGACCTAGATAACATT3'-CCTAACTGGATCTATTGTAA
5'-AGATTGACCTAGAT3'-CCTAACTGGATCTATCGTAA
5'-AGATTGACCTAGATAACATT3'-CCTAACTGGATCTATCGTAA
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Study Question 9
Bypass replication across pyrimidine dimers
generally produces which kind of base
substitution Transitions?
Transversions?
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Transitions vs Transversions
Transition G A A C
C T
Purine Purine Pyrimidine Pyrimidine
Transversion G T T
G C C C C
A C C G
Purine Pyrimidine Pyrimidine Purine
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Study Question 9
Bypass replication across pyrimidine dimers
generally produces which kind of base
substitution Transitions?
Transversions?
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Study Question 10
DNA Pol I mutant is viable. Mutation rate is
lower in mutant. If viable and lower mutation
rate, why have Pol I???
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Routes to Mutation
Base modification

• Exposure to chemical mutagen

• Reaction with base to change base pairing

HNO2
G A G T C G A G T C T C A G C T C A
U

• Replication of modified base

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Routes to Mutation
Base modification

• Exposure to chemical mutagen

G A G T C G A G T
U

• Reaction with base to change base pairing

C
T
C
A
A
C
T
C
A
G
A
G
T
C
G
A
G
T
C T C A G C T C A

• Replication of modified base

• Mutation is permanent

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Routes to Mutation
Base mimicry

• Incorporation of base mimic

G A G T C G A G T

• Replication of modified base

C
T
C
A
G
C
BrU
C
A
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Routes to Mutation
Base mimicry

• Incorporation of base mimic

G A G T C G A G T

• Replication of modified base

C T C A G C T C A
G A G T C G G G T

• Change of pairing properties (tautomerization)

C
T
C
A
G
C
BrU
C
A

• Mutation is permanent

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Problem Deamination of cytosine
Whats the threat?
C/G to T/A transition
Could you diagnose the problem?
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Strategy 3 Repair LesionSpecific Excision
Repair
Excision of base by specific glycosylase
Excision of strand by AP endonuclease
APApurinicApyrimidinic
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Study Question 11
Two mutations 1. Ura-glycosylase 2. AP
endonuclease Combine both into one
strain. Phenotype?
Phenotype of Ura-glycossylase- mutant?
Phenotype of AP endonuclease- mutant?
Phenotype of double mutant?
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Problem Error in Replication
5'-AGATTGACCTAGATTATTGTTACTGACCGCATATC-33'-TCTAA
CTGGATCTAG TAACAATGACTGGCGTATAG-5
Is it too late?
Could you diagnose the problem?
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Problem Error in Replication
5'-AGATTGACCTAGATTATTGTTACTGACCGCATATC-33'-TCTAA
CTGGATCTAGTAACAATGACTGGCGTATAG-5
Is it too late?
Could you diagnose the problem?
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Strategy 2 Repair of LesionMethyl-directed
Mismatch Repair
Old DNA strand Marked by methylation
Methylation at adenine of GATC New DNA
strand Unmarked Replication with
standard nucleotides Mark is temporary
Now can you diagnose the lesion?
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Strategy 2 Repair of LesionMethyl-directed
Mismatch Repair
MutS, H, L protein Ssb Single-stranded binding
protein
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Study Question 12
Phenotype of E. coli that cant methylate GATC?
Study Question 13
Phenotype of E. coli that overmethylates GATC?
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MutagenesisSlipped-strand mispairing
Wild-type lacI Replication Mispairing Completio
n of replication 2nd round of replication
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Study Question 4
Draw a diagram showing how mispairing could lead
to deletion of a repeat.
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Fragile X Syndrome
SQ5 Is the trait dominant? Recessive?
SQ6 Why do females have two numbers?