Lecture 10

Types of mutations

"5’----------GAATTC---------3’"

"5’----------GAATTC---------3’"

Substitutions that occur in protein-coding sequences

EXAMPLES - substitutions

Frameshift example

SNPs

SNPs

SNPs

SNPs

SNPs can have variable effects

Fate of DNA damage

Examples of mutation fixation

Human Genome

Mutation Rate per bp

Mutation rate per gene

DNA mismatch repair

MMR cont

Uracil DNA glycosylase and BER

BER

Environmental DNA damage

The discovery of NER

The process of uvrABC excision of DNA damage is called nucleotide excision repair.

NER in E. coli continued

NER in mammalian cells

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There are 8 XP complementation groups

XB Genes continued

Some XP proteins are

Cleaver’s study:  Complementation groups of XP

Developing an in vitro DNA repair system

The in vitro assay

How the incision product is detected

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Global Genomic Repair

There are endogenous and exogenous sources of mutagens

What do mutagens do?

Types of Mutagens

Alkylating agents

Reactive sites on nucleotides

Alkylating agents

Mutagens don’t always start out that way

Cytochrome P450 monooxygenase system

General reaction

Aflatoxin reaction

EMS modification of DNA

P450s are found in all cells but mostly in liver and small intestine

P450 at work

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Endogenous DNA damage

Deamination of Cytosine

Sources of exogenous DNA damage

UV Radiation,
Pyrimidine dimers

How does DNA
damage cause mutations?

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See the man pat the pet cat

Examples of repair mech’s

DNA polymerases

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Nucleotide Excision Repair

Nucleotide Excision Repair

"5’--------CCGAAttCAG-------3’"

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DNA Repair part 2

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Types of UV damage

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Nucleotide Excision Repair

How UVDE works

Mismatch repair

DNA repair diseases

Xeroderma Pigmentosum

DNA repair diseases

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