Unformatted text preview: 204-325 1 Summary of the Last Lecture Proteins are built from amino acids held together by peptide bonds. Genetic codes are triplets, comma free and nonoverlapping. The code is almost universal. Wobble base pairing contributes to the degeneracy of the code. Translation initiation involves Shine-Delgarno sequence in prokaryotes and AUG scanning in eukaryotes. Elongation of peptide chain includes repetitions of 3 steps: aminoacyl-tRNA binding, peptide bond formation, and translocation. Proteins are sorted to organelles based on their signal sequences in eukaryotes.
2 Today's Topics 1. Types of Mutations 2. Generation and Detection of Mutations 3. DNA Repair 3 Topic 1 Types of Mutations
4 Spontaneous and Random Nature of Mutations
Adaptation Induces Mutation Model X Random Mutations Give Rise to Adaptation Model 5 Somatic Vs. Germ-line Mutations 6 Purines and Pyrimidines 7 Mutations are Changes in DNA
Transition: Pu Pu Py Py Base-pair Substitution "Point" Mutation Transversion: Pu Py Py Pu Insertion/Deletion Chromosome Structure Changes Chromosomal Mutation Chromosome Number Changes
8 Transition and Transversion 9 Point Mutations within Protein Coding Sequences
Bottom strand is the template strand Silent Mutation (no change in amino acid) Neutral Missense Mutation (change to similar amino acid) Non-Neutral Missense Mutation (change from one amino acid to another) Nonsense Mutation (change from an amino acid to stop codon) Frameshift Mutation (insertion or deletion of other than 3n bp, reading frame is changed) 10 Reversion and Suppression Forward Mutation: wild type to mutant Reverse Mutation: (reversion) mutant to wild type (true reversion) or wild type like (partial reversion) by changes at the same site as the forward mutation Suppressor Mutation: mutations at a different site, intragenic or intergenic, that diminish the effect of forward mutations
11 A Nonsense Mutation Cause Translation Termination Lys 12 An Intergenic Nonsense Suppressor is a tRNA Mutation G 13 Animation 1: Nonsense Mutation and Suppression 14 Review: Types of Mutations
at DNA level at Protein level Neutral missense mutation Non-neutral missense mutation Frameshift mutation 15 Topic 2 Generation and Detection of Mutations
16 Mutagenesis: Generation of Mutations Physically Induced Spontaneous Non-Watson-Crick Addition and Deletion Chemically Induced Depurination Base Analogs Deamination Base Modifications Transposition Intercalating Ionizing Radiation (such as X-ray) UV Irradiation 17 Watson-Crick and Non-Watson-Crick Base Pairing in DNA 18 Spontaneous Mutation due to Non-Watson-Crick Base Pairing non-Watson-Crick pairing with T 19 Spontaneous Generation of Addition and Deletion 20 Depurination of Bases Causes Mutations 21 Deamination of Bases Causes Mutations 22 Mutation Hot Spots at 5mC Positions Due to Deamination 23 Production of Thymine Dimer by UV Irradiation C N 24 Base Analog 5-bromouracil (5BU) can Pair with A or G A (enol form) G 25 Mutagenic Effects of Base Analog 5-bromouracil (5BU)
5BU 5BU (rare form) (normal form) 26 Animation 2: Mutagenic Effect of 5BU 27 Deamination by Base-modifying Agent Nitrous Acid 28 Base-modification by Hydroxylation and Alkylation 29 Mutation Caused by Intercalation 30 Review: Types of Mutagenesis Physically Induced Spontaneous During Replication Ionizing Radiation:
breaks covalent bond Any Phase Chemically Induced Depurination Deamination Transposition Base Analogs Base Modifications Intercalating 31 v Non-Watson-Crick Pairing Addition Deletion UV Irradiation:
photochemical change such as T T Ames Test for Measuring Mutagenicity of Chemicals 32 Animation 3: Ames Test 33 Topic 3 DNA Repair
34 DNA Repair Systems in E. coli 35 Direct Repair of UV-induced Thymine Dimer by Photoreactivation a.k.a. "light 36 repair" Other Examples of Direct Repair Proofreading by 3' to 5' exonuclease activity of DNA polymerase III Removing alkylation damage to guanine by methyl transferase (a type of alkyltransferase) 37 Nucleotide Excision Repair (NER) of Thymine Dimmer
distortion a.k.a. "dark repair" 38 Xeroderma Pigmentosum: Defect in Excision Repair 39 Methyl Directed Mismatch Repair by Mutator Genes E. coli MutS MutL MutH Human hMSH2 hMLH1 hPMS1 hPMS2 40 Other Human Diseases Caused by Defective DNA Repair 41 Summary Changes in heritable traits result from random mutations rather than by adaptation to environmental influences. Mutations can occur in DNA spontaneously, through replication errors, or through exposure to radiation or chemical mutagens. Chemical mutagens cause mutation by acting as base analogs, by modifying bases, or by intercalating into DNA. Cells possess repair mechanisms for correcting many but not all errors in DNA.
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