Transcript Mechanisms and Analysis of DNA Mutations

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

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
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