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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 Hiroshima (Aug. 6th, 1945) (Techa River) Thymine Dimers SOS Detecting mutations with the AMES test THE AMES TEST AMES TEST 2-aminofluorene Saccharin Aflatoxin 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