Molecular Mechanisms of Mutation Flashcards
When mutations occur due to internal cellular factors, what is this called
spontaneous mutation
When mutations occur due to outer external factors, what is this called
induced mutations
Most DNA damage is caused by internal factors generated by normal metabolic processes inside the cell by…
water (hydrolysis)
oxygen (oxidation)
alkylating agents (alkylation)
What is the frequency of error in nucleotides within replication
less than 1 in a billion - it is very accurate
What is meant by mispairing due to other structures
arise through the wobble effect via flexibility in the helical structure of DNA causing base pairs to match incorrectly
OR
by protonated forms of bases
What could cause incorperated and replicated errors
tautomeric shifts or the wobble effect
What are two causes of deletions and insertions
strand slippage and unequal crossing over in meiosis
What is strand slippage
when a newly synthesized strand loops out resulting in the addition of one nucleotide on the new strand
OR
when the template strand loops out, resulting in the omission of one nucleotide on the new strand
What is unequal crossing over
exactly how it sounds
- homologous chromosomes misalign during crossing over where one crossover contains an insertion and one crossover contains a deletion
What is depurination
breakage of the covalent bond between the purine base and the 1’ carbon atom of the deoxyribose sugar
What does depurination create
an apurinic site
What is the resulting defect of depurination
no complement base can be added so a random nucleotide is incorporated (usually an A)
What is deamination
the loss of an amino group, typically from cytosine
- gives rise to uracil, which will pair with adenine during replication
- then, in the next cycle A will pair with T
*end result is a C-T transition
What is the long term result of deamination
over time, genomes become more AT rich and CG poor
What is a mutagen
an environmental agent that increases mutation rate above the spontaneous rate
What are the common classes of mutagen
base analogs
alkylating agents
deaminating chemicals
hydroxylamine
oxidative radicals
intercalating agents
radiation
What are base analogs
chemicals with structure similar to the 4 nucleotides
What is an example of a base analog
5-bromouracil (5BU) - an analog of thymine
2-aminopurine (2AP) - an analog of adenine
What are alkylating agents
mutagens that react with DNA bases and add methyl or ethyl groups