Week 12 - DNA Mutagenesis and Repair Flashcards Preview

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Flashcards in Week 12 - DNA Mutagenesis and Repair Deck (23)
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What is a mutation?

A direct altercation of a gene resulting in a new allele of that gene


Germline and Somatic Mutations

- occur in cells that produce gametes
- affects offspring of individual
- occur in somatic cells
- only affect individual
- degree of effect is linked to stage of development mutation occurs


Classes of Mutations and the type of mutations that can occur

Point Mutation
- substitution
- insertion
- deletion
Chromosomal Mutation
- inversion
- deletion
- duplication
- translocation


Types of substitution point mutations

Silent - doesn't change an amino acid but can still have phenotypic effect
Missense - change amino acid to another amino acid
Nonsense - change amino acid to stop codon


What is a Frameshift mutation?

Insertion point mutation
Deletion or insertion of a number of bases that isn't multiple of 3
Introduces premature stop codons


Forward and Reverse Mutations

Forward - loss of wild-type allele
Reverse - restores wild-type allele


Phenotypic Effects of Mutations

Loss of function mutation
- partial or total loss of functional gene product
- recessive, a diploid organism has to be homozygous for this change before the loss of protein is seen phentoypically
- e.g. cystic fibrosis
Gain of function mutation
- creation of a new trait
- hyperactivation of the protein
- often dominant
- e.g. achondroplasia


Suppressor Mutation

Mutation that hides or suppresses the effect of another mutation
- within same gene as original mutation
- can restore a reading frame
- in a different gene to original mutation
- can restore ability of gene to interact


Spontaneous Mutations - Incorrect base pairing

When a mismatched base is incorporated it will produce an error (Wobble)
When strand replicates this error is passed on creating permanent mutation


Spontaneous Mutation - Strand Slipping

One strand forms loop
Base that is looped out isn't read
Causes different strand to be produced
Strand replicated and mutation passed on


Spontaneous Chemical Changes

- loss of a purine base from a nucleotide in a DNA strand
- covalent bond breaks between purine and 1' C on deoxyribose sugar
- forms apurinic site = no template base during replication
- base randomly added
- loss of an amino group from a nitrogenous base
- e.g. cytosine to uracil
- in next round of replication, uracil pairs with adenine
- next round adenine pair with thymine
- gone from C-G to U-A to A-T


Types of Chemically Induced Mutations

Base analogues
Addition of OH groups
Alkylating agents
Intercalating agents


Chemically Induced Mutations - Base Analogues

Similar to real bases e.g. 5 bromo-uracil is uracil with 5' methyl group swapped for Br
Can from non-standard base pairs
E.g. initially binds to adenine, mispairs with guanine next replication guanine not meant to be there binds with cytosine forming mutation
U-A to C-G


Chemically Induced Mutations - Addition of Hydroxyl groups

Hydroxylamine adds OH group to cytosine
Forms hydroxylaminocytosine which binds to adenine
C-G to A-T


Chemically Induced Mutations - Alkylating agents

Add methyl or ethyl to nucleotides


Chemically Induced Mutations - Oxidation

Oxidative radicals damage DNA
E.g. 8-oxyguanine mispairs with A causing GC to TA transversion


Chemically Induced Mutations - Intercalating agents

Chemicals that insert themselves between the bases of the DNA
Distorts 3D structure
Causes single nucleotide insertions or deletions


Ionising and Non-ionising Radiation Mutations

- causes ds breaks
- e.g. x-rays, cosmic rays, gamma rays
- dislodge electrons and change stable molecules
- alter bases and break phosphodiester bonds
- UV
- bases absorb UV light
- formation of chemical bonds b/w adjacent pyrimidines e.g. thymine
- thymine dimers distort DNA
- prevents normal replication


DNA Repair Mechanisms

Mismatch repair - replication errors, mismatched bases, strand slippage
Direct repair - pyrimidine dimers
Base-excision repair - abnormal or modified bases, pyrimidine dimers
Nucleotide excision repair - DNA damage that distorts helix
Repair of ds breaks


Base Excision Repair

Removal of damaged base followed by removal of rest of nucleotide
1. DNA glycosylase enzymes detect presence of modified base
2. AP endonucleases cuts phosphodiester bond
3. Other enzymes remove sugar
4. DNA pol adds nucleotide to exposed 3' OH
5. DNA ligase repairs nick


Nucleotide Excision Repair

1. Recognise problem
2. Damaged region is made single stranded
3. Sugar-phosphate backbone of damaged strand cleaved both sides of damage
4. Excised section displaced, DNA pol replaces nucleotides and ligase seals backbone


Direct Repair

Repairs the base instead of removing it


How are ds breaks repaired?

Homologous recombination
Uses identical or nearly identical genetic information contained in another DNA molecules
Usually a sister chromatid