dna mutations and repair part 2 and 3

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