Causes of DNA Mutation - Lecture 17 Flashcards
What is a mutation?
An alteration in the nucleotide sequence of a DNA molecule
What are spontaneous mutations?
○ Mutations as a result of errors in DNA replication
○ Not common as DNA polymerases have proofreading activities
What is strand-slippage?
Scenario 1:
○ Newly synthesised strand loops out
○ New strand has an extra nucleotide
Scenario 2:
○ Template strand loops out
○ Missing a nucleotide
○ Shifts reading frame so STOP codon appears earlier
What are tautomers?
○ Isomers with slightly different chemical structures
○ Have different base-pairing properties
What do the tautomers base pair to?
○ Tautomer of A pairs with C
○ Tautomer of T pairs with G
○ Tautomer of G pairs with T
○ Tautomer of C pairs with G (no change)
What are mutagens?
Chemical or environmental agents that cause changes in DNA molecules
How can mutagens cause mutations?
○ Base analogs: chemical incorporated into DNA
○ Direct structural change e.g. UV radiation
What is 5-bromouracil?
○ An base analog of thymine
○ Used in cancer chemotherapy
○ Keto-5bU base pairs with A which is fine
○ Enol-5bU (more common) base pairs with G
What are deaminating agents?
Change the structures of some nucleotides e.g. nitrous acid and sodium bisulphite
What does deamination of the bases lead to?
○ Deamination of A gives hypoxanthine. pairs with C not T
○ Deamination of C gives uracil, pairs with A not G
○ Demainination of G gives xanthine, blocks DNA replication
○ T cannot be deaminated as it does not contain an amine group
What are alkylating agents?
○ Add alkyl groups e.g. EMS
○ Cause transition mutation
○ Adding alkyl to G makes it pair with T
What are intercalating agents?
○ Insert between base pairs e.g. ethidium bromide
○ Ethidium bromide used to visualise DNA
○ Causes insertion mutations (extra bases)
What does UV radiation cause?
○ Base dimerisation and photoproducts
○ Causes bases to interact with themselves
○ Difficult to repair as we do not have an enzyme to efficiently repair
What does heat cause?
○ Detachment of bases and gives rise to an AP site
○ AP site = apurinic or apyrimidinic
○ Easy to repair