4.1 Causes of DNA mutation

What is 5-bromouracil?

A base analog that can cause mutations by replacing thymine in a DNA molecule

What does 5-bU stand for?

5-bromouracil

What is a 6-4 photoproduct?

A dimer between 2 adjacent pyrimidine bases in a polynucleotide, formed by UV irradiation

What is an alkylating agent?

A mutagen that acts by adding alkyl groups to nucleotide bases 

What is an AP site? (complete definition)

A position in a DNA molecule where the base component of the nucleotide is missing

What is a base analog?

A compound whose structural similarity to one of the bases in DNA enables it to act as a mutagen 

What is a baseless site?

A position in a DNA molecule where the base component of the nucleotide is missing 

What is a cyclobutyl dimer?

A dimer between two adjacent pyrimidine bases in a polynucleotide, formed by UV irradiation

What is a deaminating agent?

A mutagen that acts by removing amino groups from nucleotide bases

What is ethidium bromide?

A type of intercalating agent that causes mutations by inserting between adjacent base pairs in a double stranded DNA molecule

What is a tautomer?

Structural isomers that are in dynamic equilibrium

What is a photoproduct?

A modified nucleotide resulting from treatment of DNA with UV radiation

What is a mutagen?

A chemical or physical agent that can cause a mutation in DNA molecule 

What is ethylmethane sulfonate?

A mutagen that acts by adding alkyl groups to nucleotide bases

What does EMS stand for?

Ethylmethane sulfonate

What is an intercalating agent?

A compound that can enter the space between adjacent base pairs of a double-stranded DNA molecule, often causing mutations 

What type of mutation are ‘errors in DNA replication’?

Spontaneous

Why are spontaneous mutations not common?

Bc most DNA polymerases have proofreading activities so are very accurate

What are the 2 ways in which mutations can occur?

Errors in DNA replication / Mutagen 

How does replication errors occur?

DNA polymerase making a mistake 

What are the 2 ways in which replication errors occur?

Strand slippage / tautomeric shifts

What does strand slippage result in?

Missing or extra nucleotides

What regions of DNA are prone to strand slippage?

Regions of DNA containing many copies of small repeated sequences

What are most DNA replication mistakes caused by?

Base tautomerism

What does amino-adenine base pair with?

T 

What does keto-thymine base pair with?

A

What does keto-guanine base pair with?

C

What does amino-cytosine base pair with?

G

What does imino-adenine base pair with?

C

What does enol-thymine base pair with?

G

What does enol-guanine base pair with?

T

What does imino-cytosine base pair with?

G

What is the less common tautomer of amino-adenine?

Imino-adenine

What is the less common tautomer of keto-thymine?

Enol-thymine

What is the less common tautomer of keto-guanine? 

Enol-guanine 

What is the less common tautomer of amino-cytosine?

Imino-cytosine

What is the normal base for the tautomer imino-adenine?

Amino-adenine

What is the normal base for the tautomer enol-thymine?

Keto-thymine

What is the normal base for the tautomer enol-guanine?

Keto-guanine

What is the normal base for the tautomer imino-cytosine?

Amino-cytosine 

What are the 2 ways in which mutagens can cause mutations?

Base analogs / Direct structural change

What is an important base analog to know?

5-bromouracil /5bU

What is 5bU an analog of?

Thymine

Which between keto-5bU and enol-5bU is more common? and why is it a problem?

Enol-5bU, replaces T but pairs with G not A

What agent can cause changes in the structure of some nucleotides?

Deaminating / alkylating / Intercalating

What do alkylating agents do?

Add alkyl groups 

What do deaminating agents do?

Remove amine groups

What are some examples of deaminating agents?

Nitrous acid / sodium disulphite

What does the deamination of adenine produce?

Hypoxanthine

What does Hypoxanthine base pair with?

C

What is ‘deaminating’

Removal of an amine group (NH2)

What does the deamination of cytosine produce?

Uracil 

What does the deamination of guanine produce?

Xanthine

What does xanthine do?

Blocks DNA replication

Why is thymine not deaminated?

Doesn’t contain amine group

Which bases does not contain an amine group?

Thymine / uracil

Which DNA bases does not contain an amine group?

Thymine 

Which RNA bases does not contain an amine group?

Uracil

What is an example of an alkylating agent?

Ethylmethane sulphonate / EMS

Which type of mutation does alkylating agents cause?

Transition mutation 

Which base is alkylated to produce O6-ethylguanine?

Guanine 

What does the alkylation of guanine produce?

O6-ethylguanine 

What does O6-ethylguanine base pair with?

T

What do intercalating agents do?

Insert between base pairs

What is an example for a intercalating agent?

Ethidium bromide

What type of mutation do intercalating agents cause?

Insertion mutation 

What does ‘intercalating’ mean?

'Go in between’

What does UV radiation cause?

Base dimerization / photoproducts

How does heat cause mutation?

Causes detachment of bases, give rise to an AP site

How is a base detached by heat?

Heat-induced hydrolysis of a B-N-glycosidic bond