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Protein Synthesis and Mutation

Protein Synthesis and Mutation. Gene Regulation in Prokaryotes Mutation(Permanent, heritable DNA changes) Point mutation (base substitutions) Missense mutation Nonsense mutation (premature stop) Silent mutation Insertions/deletions Frameshift mutation Dramatic change in amino acids

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Protein Synthesis and Mutation

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  1. Protein Synthesis and Mutation • Gene Regulation in Prokaryotes • Mutation(Permanent, heritable DNA changes) • Point mutation (base substitutions) • Missense mutation • Nonsense mutation (premature stop) • Silent mutation • Insertions/deletions • Frameshift mutation • Dramatic change in amino acids • Run-ons, premature stops (nonsense mut.) • The Creation of Mutation (mutagenesis) • Spontaneous mutation • Occurs in DNA replication (1 in 109 bp) • Chemical mutagens • Base pair changers (nitrous acid) • Base analogues (e.g.. 5 bromouracil) • Frameshift mutagens (aflatoxin, benzpyrene) • Radiation • X rays, gamma rays break DNA, bases • UV light causes knots in DNA strand Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.

  2. Genes in Prokaryotes Are Grouped Together and Regulated Together Repressible operon of genes (normally “on”) Used to regulate genes that are used all the time, like amino acid making genes Inducible operon of genes (normally “off”) Used in “rainy day” gene sets like for lactose utilization

  3. Mutation: Some Definitions • A heritable change in the genetic material • Mutations may be neutral, beneficial, or harmful • Mutagen: Agent that causes mutations • Spontaneous mutations: Occur in the absence of a mutagen

  4. Mutation: Base Substitution (Point Mutations) G G C C Glu (a) Silent mutation (d) Run-on mutation

  5. Regulation of Bacterial Gene Expression • Steps in Translation of mRNA • Initiation, Elongation, Termination • Mutation(Permanent, heritable DNA changes) • Point mutation (base substitutions) • Missense mutation • Nonsense mutation (premature stop) • Silent mutation • Insertions/deletions • Frameshift mutation • Dramatic change in amino acids • Run-ons, premature stops (nonsense mut.) • The Creation of Mutation (mutagenesis) • Spontaneous mutation • Occurs in DNA replication (1 in 109 bp) • Chemical mutagens • Base pair changers (nitrous acid) • Base analogues (e.g.. 5 bromouracil) • Frameshift mutagens (aflatoxin, benzpyrene) • Radiation • X rays, gamma rays break DNA, bases • UV light causes knots in DNA strand Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.

  6. Mutation: Insertions and Deletions THEBIGCATATETHERAT THEBIGCBATATETHERAT Figure 8.17a, d

  7. Summary of Mutation Types Run-on mutation Stop codon lost so protein is extra long (can also produce nonsense and run-ons)

  8. Protein Synthesis and Mutation • Steps in Translation of mRNA • Initiation, Elongation, Termination • Mutation(Permanent, heritable DNA changes) • Point mutation (base substitutions) • Missense mutation • Nonsense mutation (premature stop) • Silent mutation • Insertions/deletions • Frameshift mutation • Dramatic change in amino acids • Run-ons, premature stops (nonsense mut.) • The Creation of Mutation (mutagenesis) • Spontaneous mutation • Occurs in DNA replication (1 in 109 bp) • Chemical mutagens • Base pair changers (nitrous acid) • Base analogues (e.g.. 5 bromouracil) • Frameshift mutagens (aflatoxin, benzpyrene) • Radiation • X rays, gamma rays break DNA, bases • UV light causes knots in DNA strand Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.

  9. Spontaneous and Induced Mutation • Spontaneous mutation rate = 1 in 109 (a billion) replicated base pairs or 1 in 106 ( a million) replicated genes. Mistakes occur during DNA Replication just before cell division. This is natural error rate of DNA polymerase. • Mutagens increase mistakes to to 10–5 (100 thousand) or 10–3 ( a thousand) per replicated gene

  10. Chemical Mutagens Base pair altering chemicals (base modifiers) deaminators like nitrous acid, nitrosoguanidine, or alkylating agents like cytoxan Nitrous acid cytoxan Base analogues “mimic” certain bases but pair with others - E.g. 5-fluorouracil, cytarabine Acts like a “C” Incorporated as a “T” cytarabine

  11. Chemical Frameshift Mutagens Intercalate into DNA Carboplatin (anti-cancer drug) Benzpyrene in cigarette smoke Aflatoxin from Aspergillus fungus growing on corn Daunarubicin (anti-cancer drug) ATGCCGTAGCCG ATGC TAGCCG ATGCTAGCCG Bleomycin (anti-cancer drug produced by Streptomyces)

  12. Protein Synthesis and Mutation • Steps in Translation of mRNA • Initiation, Elongation, Termination • Mutation(Permanent, heritable DNA changes) • Point mutation (base substitutions) • Missense mutation • Nonsense mutation (premature stop) • Silent mutation • Insertions/deletions • Frameshift mutation • Dramatic change in amino acids • Run-ons, premature stops (nonsense mut.) • The Creation of Mutation (mutagenesis) • Spontaneous mutation • Occurs in DNA replication (1 in 109 bp) • Chemical mutagens • Base pair changers (nitrous acid) • Base analogues (e.g.. 5 bromouracil) • Frameshift mutagens (aflatoxin, benzpyrene) • Radiation • X rays, gamma rays break DNA, bases • UV light causes knots in DNA strand Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.

  13. Mutation: Ionizing Radiation • Ionizing radiation (X rays, gamma rays, UV light) causes the formation of ions that can react with nucleotides and the deoxyribose-phosphate backbone. • Nucleotide excision repairs mutations

  14. X-rays and Gamma Rays Cause Breaks in DNA

  15. Ionizing Radiation: UV • UV radiation causes thymine dimers, which block replication. • Light-repair separates thymine dimers • Sometimes the “repair job” introduces the wrong nucleotide, leading to a point mutation. Figure 8.20

  16. RecA Mismatch and SOS/”Light” Repair: Error Prone

  17. Protein Synthesis and Mutation • Steps in Translation of mRNA • Initiation, Elongation, Termination • Mutation(Permanent, heritable DNA changes) • Point mutation (base substitutions) • Missense mutation • Nonsense mutation (premature stop) • Silent mutation • Insertions/deletions • Frameshift mutation • Dramatic change in amino acids • Run-ons, premature stops (nonsense mut.) • The Creation of Mutation (mutagenesis) • Spontaneous mutation • Occurs in DNA replication (1 in 109 bp) • Chemical mutagens • Base pair changers (nitrous acid) • Base analogues (e.g.. 5 bromouracil) • Frameshift mutagens (aflatoxin, benzpyrene) • Radiation • X rays, gamma rays break DNA, bases • UV light causes knots in DNA strand Proteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.

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