DNA Mutations and Repair

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Presentation transcript:

DNA Mutations and Repair Chapter 18

Mutation Rates and Frequency 1 to 10 mutations per million gametes Incidence within a group

Causes of Mutations Spontaneous Induced

Spontaneous Mispairing of bases Changes in chemical structure of DNA

Tautomers

But this is probably a much more common occurrence. A spontaneous error

Spontaneous Incorporated Error (perhaps due to wobble) To Replicated Errors A replicated Error

Chemical changes to the DNA Depurination Deamination

Depurination Chemical change in the DNA

NH2 is gone DNA Repair

Naturally Occurring NO REPAIR!

Environmentally Induced DNA changes

Chemicals and Reactions Leading to Mutations Base analogs Alklating agents Deaminations Hydroxylamine Oxidative reactions Intercalating agents

Mistake!!

alklyating Deamination Adds OH

Mustard Gas: alkylating agent

Oxidative radicals Reactive forms of oxygen can lead to these radicals

Intercalating agents Insert and distort DNA

Radiation (Techa River) Hiroshima (Aug. 6th, 1945)

Thymine Dimers SOS

Detecting mutations with the AMES test

THE AMES TEST

AMES TEST Saccharin Aflatoxin 2-aminofluorene

Aflatoxin B1

DNA Repair: general characteristics Double stranded DNA Redundancy of pathways

Types of DNA repair Mismatch repair Direct Repair Base-Excision Repair Nucleotide Excision Repair

Mismatch repair Mut H Recognize GATC hemi-methylation Mut S Mut L

A closer look at mismatch repair

DIRECT REVERSAL REPAIR Direct Repair

BASE EXCISION REPAIR

BASE EXCISION REPAIR

Nucleotide Excision Repair

Diseases of DNA repair!

Xeroderma pigmentosum Autosomal recessive

Hereditary Non-Polyposis Colon Cancer HNPCC 15% of all colon cancers

Li-Fraumeni P-53 mutation