Lectures 5 and 6: Mechanisms of Mutation Flashcards
What is genetic variation?
The differences in the DNA sequence of individuals in a population
What are mutations?
Random events that occur due to environmental factors or failure of repair
Can mutations be repaired?
Yes
Define Mutation:
A change in the DNA sequence that arises de novo in an individual or tissue
Define Polymorphism:
A germline DNA sequence variation that can be stably inherited
What are the external factors that cause mutations?
- Mutagens like radiation and chemicals which cause depurination, demethylation and deamination
- Presence of Base Analogues
How do external factors cause mutations?
They can cause direct structural effects or act indirectly by causing cells to produce other chemicals that have an effect
What are the internal factors that cause mutations?
- Replication errors
- Replication must be faithful otherwise accumulated deleterious mutations would be incompatible with life
What are tautomers?
Isomers of a compound that exist in equilibrium
The stable form of T and G is the ______ form, the unstable form is the ______ form.
Keto
Enol
The stable form of A and C is the ______ form, the unstable form is the ______ form.
Amino
Imino
Unstable tautomers can form _____________.
Unstable pairs (i.e A-C or T-G)
What is a mutagen?
An agent that causes an increase in the rate of mutation by causing chemical changes to the bases
Deamination can be induced by _______ or occur _______________.
HNO2 or occur spontaneously
When cytosine is deaminated we get __________. When 5-methylcytosine is deaminated we get __________.
Uracil
Thymine
What do alkylating agents do?
Donate their alkyl groups to other molecules, this can cause transitions, transversions, frameshifts and chromosome aberrations
With respect to bases, what is a transition?
Change from one purine to another or from one pyrimidine to another
With respect to bases, what is a transversion?
Change from a purine to a pyrimidine
What is depurination?
The loss of a base caused by the hydrolysis of the N-glycosidic bond of a purine ring that binds to the sugar part of the nucleotide. The base is replaced at random
What is a base analogue?
A compound with similar structure to the normal bases but causes an increase in the freq. of mutations
What is 2-aminopurine?
An analogue of adenine that pairs with cytosine
What is 5-bromouracil?
An analogue of thymine that pairs with guanine
What are intercalating agents?
Thin plate-like hydrophobic molecules that insert themselves between adjacent bases, they are usually +’vely charged
What does ionising radiation do?
Breaks covalent bonds between bases and causes chromosome aberrations
