DNA Mutations and Repairpart 2 and 3Chapter 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)
A replicated Error
To Replicated Errors
Chemical changes to the DNA
Depurination
Deamination
Depurination
Chemical change in the DNA
NH2 is gone
DNA Repair
NO REPAIR!
Naturally Occurring
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
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 DimersSOS
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 Repair
DIRECT REVERSAL REPAIR
BASE EXCISION REPAIR
BASE EXCISION REPAIR
Nucleotide Excision Repair
Diseases of DNA repair!
Xeroderma pigmentosumAutosomal recessive
Hereditary Non-Polyposis Colon Cancer HNPCC
15% of all colon cancers
Li-Fraumeni P-53 mutation