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Protein Synthesis and Mutation






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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
Protein Synthesis and Mutation

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Slide 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.

Slide 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

Slide 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

Slide 4

Mutation: Base Substitution (Point Mutations)

G

G

C

C

Glu

(a) Silent mutation

(d) Run-on mutation

Slide 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.

Slide 6

Mutation: Insertions and Deletions

THEBIGCATATETHERAT

THEBIGCBATATETHERAT

Figure 8.17a, d

Slide 7

Summary of Mutation Types

Run-on mutation

Stop codon lost so protein is extra long

(can also produce nonsense and run-ons)

Slide 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.

Slide 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

Slide 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

Slide 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)

Slide 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.

Slide 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

Slide 14

X-rays and Gamma Rays Cause Breaks in DNA

Slide 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

Slide 16

RecA

Mismatch and SOS/”Light” Repair: Error Prone

Slide 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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