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G e n e t i c s N e w s. Mutation - Overview. Mechanism of mutation Spontaneous Induced. Duplication/Insertions Mechanism (example: lacI ) Fragile X syndrome. Repair of mutation Bypass replication Excision repair Mismatch repair. Mutation and its Avoidance. Thrust. Parry. - PowerPoint PPT Presentation
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Genetics News
Mutation - OverviewMechanism of mutation
SpontaneousInduced
Duplication/InsertionsMechanism (example: lacI)
Fragile X syndrome
Repair of mutationBypass replicationExcision repairMismatch repair
Mutation and its Avoidance
Thrust
DNA damage
Base substitution
Base mimicry
Intercalation
Parry
Reversal of lesion
Bypass of lesion
General excision pathway
Specific excision pathway
Mismatch repair pathway
UV
Pyrimidine dimers
T-T C-T T-C
Routes to MutationDNA Damage
Light
Repair Strategy #1Reversal of mutation
DNA photolyase
DNA Polymerase III
Faithful Error-correcting
SOS response
Induced by DNA damage Elicits repair enzymes Recruits DNA Pol I
Repair Strategy #2Bypass of mutation
Modified DNA Polymerase III
Resourceful Innovative
Repair Strategy #2Bypass of mutation
SOS-induced genes
Modified DNA Polymerase III
Resourceful Innovative
5'-AGATTGACCTAGAT3'-CCTAACTGGATCTATTGTAA5'-AGATTGACCTAGATAACATT3'-CCTAACTGGATCTATTGTAA5'-AGATTGACCTAGAT3'-CCTAACTGGATCTATCGTAA5'-AGATTGACCTAGATAACATT3'-CCTAACTGGATCTATCGTAA
Repair Strategy #2Bypass of mutation
When in doubt, A
Study Question 9
Bypass replication across pyrimidine dimers generally produces which kind of base substitution:
Transitions? Transversions?
Transitions vs Transversions
Transition:
G A A C C T
Transversion:
G T T G C C
C C A C C G
Purine Purine; Pyrimidine Pyrimidine
Purine Pyrimidine; Pyrimidine Purine
Study Question 9
Bypass replication across pyrimidine dimers generally produces which kind of base substitution:
Transitions? Transversions?
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???
Routes to Mutation
G A G T C G A G T C T C A G C T C A
HNO2
U
Base modification
• Exposure to chemical mutagen
• Reaction with base to change base pairing
• Replication of modified base
Routes to Mutation
G A G T C G A G TU
Base modification
• Exposure to chemical mutagen
• Reaction with base to change base pairing
C T C A G C T C A
• Replication of modified baseG A G T C G A G T
C T C A A C T C A
• Mutation is permanent
Routes to Mutation
G A G T C G A G T
Base mimicry
• Incorporation of base mimic
• Replication of modified baseC T C A G CBrU C A
Routes to Mutation
G A G T C G A G T
Base mimicry
• Incorporation of base mimic
• Replication of modified base
• Mutation is permanent
G A G T C G G G T
C T C A G CBrU C A
C T C A G C T C A
• Change of pairing properties (tautomerization)
Problem: Deamination of cytosine
What’s the threat? C/G to T/A transition
Could you diagnose the problem?
Strategy #3: Repair LesionSpecific Excision Repair
Excision of base by specific glycosylase
Excision of strand by AP endonuclease
APApurinic
Apyrimidinic
Study Question 11Two mutations:
1. Ura-glycosylase2. AP endonuclease
Combine both into one strain.
Phenotype?
Phenotype of Ura-glycossylase- mutant?
Phenotype of AP endonuclease- mutant?
Phenotype of double mutant?
Problem: Error in Replication
5'-AGATTGACCTAGATTATTGTTACTGACCGCATATC-3’3'-TCTAACTGGATCTAG TAACAATGACTGGCGTATAG-5’
Is it too late?
Could you diagnose the problem?
Problem: Error in Replication
Is it too late?
Could you diagnose the problem?
5'-AGATTGACCTAGATTATTGTTACTGACCGCATATC-3’3'-TCTAACTGGATCTAGTAACAATGACTGGCGTATAG-5’
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?
Strategy #2: Repair of LesionMethyl-directed Mismatch Repair
MutS, H, L: protein
Ssb: Single-stranded binding protein
Study Question 12
Phenotype of E. coli that can’t methylate GATC?
Study Question 13Phenotype of E. coli that overmethylates GATC?
MutagenesisSlipped-strand mispairing
Wild-type lacI
Replication
Mispairing
Completion of replication
2nd round of replication
Study Question 4
Draw a diagram showing how mispairing could lead to deletion of a repeat.
Fragile X Syndrome
SQ5: Is the trait dominant? Recessive?
SQ6: Why do females have two
numbers?