Mutation Point Mutations Spontaneous Induced Depurination Deamination

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Presentation transcript:

Mutation Point Mutations Spontaneous Induced Depurination Deamination Oxidatitive damage Replication errors Trinucleotide repeat expansion and human disease Induced Base analogs Base modifiers Base damagers (DNA damage) Ames Test for Mutagens (because some mutagens = carcinogens)

Spontaneous Mutations: Depurination

Depurination: Mutagenesis by SOS-mediated repair

Spontaneous Deamination: Cytosine to Thymine 5 methyl C’s Are hot spots For mutations

Spontaneous Mutations: Oxidative damage G-C to T-A transversions

Spontaneous Replication Errors: Amino to Imino Cytosine G-C to A-T and A-T to G-C transitions

Spontaneous Replication Errors: Keto to Enol Thymine A-T to G-C and G-C to A-T transitions

Spontaneous Replication Errors: Amino to Imino Adenine A-T to G-C and G-C to A-T transitions

Spontaneous Replication Errors: Keto to Enol Guanine G-C to A-T and A-T to G-C transitions

Spontaneous INDEL Mutations: insertion or deletion of one to a few bps Slippage and mispairing in repeat-rich sequences “hot spots” for indel mutations

Trinucleotide Repeat Expansions: Fragile-X syndrome

Induced Mutations: Base Analogs: 5 BU (5BrdU)

Induced Mutations: Base Analogs: 2-AP (2 aminopurine)

Induced Mutations: Base Modifiers: EMS and NG (ethylmethansulfonate and nitrosoquanidine)

Induced Mutations: Intercalating Drugs (intercalating dyes)

Induced Mutations: UV Light

Experimental Test for Mutagens: the Ames Test

Induced Mutations: AFB1 and G-C to T-A transversions

Example Results of the Ames Test TA100: requires a missense TA1538: requires a frame shift

Summary of Spontaneous and Induced Mutations Imino C pairs with A: G-C to A-T transition A-T to G-C Enol T pairs with G: A-T to G-C G-C to A-T Imino A pairs with C: A-T to G-C Enol G pairs with T: G-C to A-T Ionized 5 BU pairs with G: A-T to G-C Protonated 2-AP pairs with C: A-T to G-C 0-6 ethyl guanine pairs with T G-C to A-T Aflatoxin-mediated depurination of G: G-C to T-A transversion