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G e n e t i c s N e w s

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.

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G e n e t i c s N e w s

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  1. GeneticsNews

  2. Mutation - Overview Mechanism of mutation Spontaneous Induced Duplication/Insertions Mechanism (example: lacI) Fragile X syndrome Repair of mutation Bypass replication Excision repair Mismatch repair

  3. 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

  4. Routes to Mutation DNA Damage UV Pyrimidine dimers T-T C-T T-C

  5. Repair Strategy #1 Reversal of mutation Light DNA photolyase

  6. 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

  7. Repair Strategy #2 Bypass of mutation SOS-induced genes Modified DNA Polymerase III Resourceful Innovative

  8. 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

  9. Study Question 9 Bypass replication across pyrimidine dimers generally produces which kind of base substitution: Transitions? Transversions?

  10. Transitions vs Transversions Transition: G A AC C T Purine Purine; Pyrimidine Pyrimidine Transversion: G TT G CCC C A C C G Purine Pyrimidine; Pyrimidine Purine

  11. Study Question 9 Bypass replication across pyrimidine dimers generally produces which kind of base substitution: Transitions? Transversions?

  12. 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???

  13. 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 TC T C A G C T C A U • Replication of modified base

  14. 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

  15. 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

  16. 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

  17. Problem: Deamination of cytosine What’s the threat? C/G to T/A transition Could you diagnose the problem?

  18. Strategy #3: Repair LesionSpecific Excision Repair Excision of base by specific glycosylase Excision of strand by AP endonuclease APApurinicApyrimidinic

  19. 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?

  20. Problem: Error in Replication 5'-AGATTGACCTAGATTATTGTTACTGACCGCATATC-3’3'-TCTAACTGGATCTAGTAACAATGACTGGCGTATAG-5’ Is it too late? Could you diagnose the problem?

  21. Problem: Error in Replication 5'-AGATTGACCTAGATTATTGTTACTGACCGCATATC-3’3'-TCTAACTGGATCTAGTAACAATGACTGGCGTATAG-5’ Is it too late? Could you diagnose the problem?

  22. 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?

  23. Strategy #2: Repair of LesionMethyl-directed Mismatch Repair MutS, H, L: protein Ssb: Single-stranded binding protein

  24. Study Question 12 Phenotype of E. coli that can’t methylate GATC? Study Question 13 Phenotype of E. coli that overmethylates GATC?

  25. MutagenesisSlipped-strand mispairing Wild-type lacI Replication Mispairing Completion of replication 2nd round of replication

  26. Study Question 4 Draw a diagram showing how mispairing could lead to deletion of a repeat.

  27. Fragile X Syndrome SQ5: Is the trait dominant? Recessive? SQ6: Why do females have two numbers?

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