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 mutationsCategories 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

3. Frameshift mutations

4. Expanding trinuleotide repeats

Lead to

Gene Mutations can also be classified by type of mutation

Base Substitutions

Transitions and Transversions

can be

PURINE TO PURINEPURINE 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

Reverse mutationForward mutation

Forward versus Reverse Mutations

Terms associated with PHENOTYPIC effects of mutations on protein structure

Phenotypic effects can also change function

1 Sullivan, J.P. et al., Department of Pathology, College of Veterinary Medicine, 1998 The University of Georgia, Athens, GA

Gain of Gene Function1

Loss of Gene Function2

Qualtek Molecularlabs Web Site

or

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 DimersSOS

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 TESTSalmonella typimurium

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

The End