Lecture 17 Causes of Mutations Flashcards
Defne a mutation
A Mutation is an alteration in the nucleotide sequence of a DNA molecule
State the two ways in which DNA mutations can occur
1) Spontaneous mutations caused by errors in DNA replication
2) Can be caused by mutagens
Define and explain Base tautomerism
Occurs when DNA polymerase is tricked due to tautomers.
Define tautomer
Isomers of the nucleotide bases. Isomers have slightly different chemical structures.
Define tautomeric shift
- Amino adenine isomerizes to form imino adenine.
- Usually A pairs with T but Iminio-adenine base pairs with C.
- So you get an AC base pair which is a mutation.
- Polymerase cannot distinguish between amino-adenine and imino-adenine.
List the full names of the 4 bases
- Amino-adenine(AT)
- Keto-thymine (TA)
- Keto-guanine (GC)
- Amino-cytosine (CG)
List the full names of the less common tautomers for the 4 DNA bases.
Imino Adenine (pairs with C) Enol Thymine (pairs with G) Enol Guanine (pairs with T) Imino Cytosine (pairs with G)
Define mutagens
Mutagens are chemical or environmental agents that cause changes in DNA molecules.
How many important ways can mutagens cause mutations to the DNA
2 main pathways by which mutagens cause mutations (either chemical - act as base analogues or environmental - direct damage)
State the two ways in which mutagens can cause mutations
Mutagens will either be chemical agents like a de-aminating agent or environmental agents like UV and heat
State an important base Analog
5-bromouracil 5bu
5bU is an analog of thymine.
How do base analogs cause DNA mutations
- Base analogs mimic the base pairs
- During replication these base analogs can get incoroporated into the DNA
Give the name of an important example of a Base Analog
5 BromoUracil (5bU)
Of which DNA base is 5-Bromo Uracil an analogue of, and which chemical group is different.
I-t is an analogue of Thymine.
- The Methyl group on Thymine is replaced by a Bromine.
How does 5-Bromo Uracil differ from Thymine
The methyl group is replaced by a Bromine.
Why does the tautomer 5-B-u not cause mutation?
- Keto-5-Bu will replace T
- Keto 5 Bromo Uracil will base pair with Adenine, as normal.
- Thus if incorporated into the DNA instead of Thymine, this is fine.
- Thus there is no change t
Which tautomeric form of 5 Bromo Uracil exhibits mutagenic effects
Enol-5 Bromo Uracil
State the names of the two forms of 5- Bromo Uracil
- Keto 5 Bromo Uracil
- Enol 5 Bromo Uracil
Why does Enol 5 Bromo Uracil cause mutation while Keto Bromo Uracil does not.
Because Enol 5- Bromo Uracil base pairs with Guanine but Keto 5 Bromo Uracil will base pair with Adenine.
Which base pair does Enol 5 Bromo Uracil base pair with
Guanine
Which base pair does Keto 5 Bromo Uracil base pair with
Adenine.
Nitrous acid and sodium buslphite are ….
Deaminating agents
State an example of common chemical mutagen
Deaminating agents
What happens when Adenine undergoes deamination
Produces Hypoxanthine.
Which base pair does Hypoxanthine form
Hypoxanthine base pairs with cytosine.
Apple Tart
Hypoxy Chocolate
Remember this mnemonic
Deamination of Cytosine results in ….
Uracil.
Uracil pairs with Adenine.
results in alteration in nucleotide sequence from a G to A.
Deamination of Guanine
Xanthine.
What does Xanthine do
Blocks DNA replication
Summarise the effect of de-amination on
i) Adenine
ii) Cytosine
iii) Guanine
i ) Adenine turns to hypo-xanthanine
ii ) Cytosine turns to Uracil
iii) Guanine turns to Xanthine
Which bases are purine bases
Adenine and Guanine
Which bases are pyrimidine bases
Cytosine and Thymine and Uracil
How many rings in purines
2 ringed bases
How many rings in pyrimidines
1 ring
What is an alkylating agent
Alkylating agents add alkyl groups
Name an example of an alkylating agent
Ethylmethane Sulphonate (EMS)
What is Ethlymethane Sulphonate an example of
an Alkylating agent which is a mutagen
Name an example of an intercalating agent
Ethidium bromide
How does an intercalating agent work to cause mutations
Intercalating agents insert themselves between the base pairs.
What does Ethidium bromide do
Inserts itself between base pairs.
What does UV light do do DNA
UV radiation causes base dimerization. (eg causes two molecules of the same base to react in an addition reaction forming an adduct.
What are the products of UV induced base dimerization of Thymine
- Cyclobutyl dimer
- B 6,4 photoproduct.
What is the effect of heat on DNA
- heat causes hydrolysis of bases
- which causes a gap in the DNA.
State the hardest type of DNA mutation to repair
When UV Light causes dimerization of Thymine to produce a 6,4 photoproduct.