Download Ch. 17 DNA mutations and Repair

DNA Mutations and Repair
Chapter 17
Mutation: is defined as an inherited
change in genetic information by cell
division or individual organisms.
Chernobyl, April 26th, 1986
Mutations can be classified into categories.
Categories of mutations
Somatic and germ line
Achondroplasia
Autosomal Dominant
Gene Mutations can also be classified by type of mutation

1. Base Substitutions
□ 2. Insertions and deletions
Lead to

3. Frameshift mutations

4. Expanding trinuleotide repeats
Gene Mutations can also be classified by type of mutation

Base Substitutions
can be
Transitions and Transversions
PURINE TO PURINE
PURINE TO PYRIMIDINE
PYRIMIDINE TO PURINE
Expanding trinucleotide repeats
Fragile X Syndrome
Pre-mutation
Fragile X syndrome:FMR-1 gene
Strand slippage may cause repeats
Phenotypic changes and mutations
Forward mutation
Reverse mutation
Forward versus Reverse Mutations
Terms associated with PHENOTYPIC effects of mutations on protein structure
Phenotypic effects can also change function
Gain of Gene Function
1
1
Sullivan, J.P. et al.,
Department of Pathology,
College of Veterinary Medicine, 1998
The University of Georgia, Athens, GA
or
Loss of Gene Function
Qualtek Molecularlabs Web Site
2
Loss of Function can also occur!
Typically recessive mutations!
Suppressor Mutations is a genetic change that hides the
effect of another mutation
Intragenic Suppressor Mutations
Intergenic Mutation
Lethal Mutations
Do you remember something about each type of mutation?
This is easy!
Mutation Rates and Frequency
1 to 10 mutations per million gametes
Incidence within a group
Causes of Mutations
Spontaneous
Induced
Environmentally Induced DNA changes
Intercalating agents

Insert and distort DNA
Radiation
Hiroshima (Aug. 6th, 1945)
(Techa River)
Thymine Dimers
SOS
Chemicals and Reactions Leading to Mutations
alklyating
Deamination
Adds OH
Oxidative radicals

Reactive forms of
oxygen can lead to
these radicals
Detecting mutations with the AMES test
THE AMES TEST Salmonella typimurium
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
The End