Mod 8- Causes Of DNA Mutation & DNA Repair Flashcards
What is a mutation?
An alteration in the nucleotide sequence of a DNA molecule.
What are spontaneous mutations?
Mutations that result from errors in DNA replication.
What causes strand-slippage during DNA replication?
Regions of DNA containing many copies of small repeated sequences.
This is when it loops out to add or remove a nucleotide (causing frame shift)
What is base tautomerism?
A phenomenon where a DNA polymerase is tricked by isomers with slightly different chemical structures.
What is an important base analog used in mutation studies?
5-bromouracil (5bU).
What does 5-bromouracil (5bU) mimic?
Thymine.
What is the consequence of enol-5bU pairing incorrectly during replication?
It pairs with G instead of A.
What are mutagens?
Chemical or environmental agents (radiation/ UV light) that cause changes in DNA molecules.
What is the effect of deaminating agents on adenine?
Deamination of adenine gives hypoxanthine, which pairs with C not T.
What does deamination of cytosine produce?
Uracil, which pairs with A not G.
What are alkylating agents?
Agents that add alkyl groups to nucleotides.
Name an example of an alkylating agent.
Ethylmethane sulphonate (EMS).
Causes transition mutation
What type of mutation do intercalating agents cause?
Insertion mutations.
What is an example of an intercalating agent?
Ethidium bromide.
What type of DNA damage is caused by ultraviolet radiation?
Causes bases to interact with themselves
Base dimerization- bases connect to each other
Photoproducts.
What is an AP site?
Apurinic, apyrimidinic site resulting from the detachment of bases.
How often does depurination or depyrimidination occur?
About 1000 times a day.
True or False: Thymine can be deaminated.
False.
Fill in the blank: Deamination of guanine gives _______.
xanthine.
This blocks DNA replication as it can’t base pair with anything
What effect does heat have on DNA?
Causes detachment of bases, leading to an AP site.
What is the primary importance of DNA repair?
Preserving the composition and coding potential of the genome
What is direct repair in the context of DNA mutations?
An enzyme corrects a nucleotide alteration caused by a mutagen
Which enzyme in E. coli can remove alkyl groups from nucleotides?
ADA enzyme
Removes alkyl groups attached to position 4 of T and position 6 of G
What is the function of the MGMT enzyme in humans?
Removes alkyl groups from position 6 of G
What type of DNA damage can be repaired by DNA photolyase in E. coli?
Base dimers formed by UV radiation
What is the nucleotide excision repair system?
Damaged nucleotide is removed and the gap is filled by DNA synthesis
What are the two types of excision repair?
- Base excision repair- a single altered base is removed
- Nucleotide excision repair- a longer piece of DNA containing the altered bases is removed
How does base excision repair happen in E. coli?
Begins with removal of the damaged base by a DNA glycosylase enzyme
Heat gives rise to an AP site
AP site is then filled
What does AP stand for in the context of DNA damage?
Apurinic, apyrimidinic site
What enzyme carries out nucleotide excision repair in E. coli?
UvrABC endonuclease
The region containing the damaged nucleotide is excised and resynthesised
What distinguishes the parent strand from the daughter strand during mismatch repair in E. coli?
The parent strand is methylated
Which enzymes recognize mismatches in E. coli?
- MutH
- MutS
The mismatch is excised and the DNA is resynthesised
How does mismatch repair in humans differ from that in E. coli?
Humans do not involve methylation and use MutS-like proteins for mismatch recognition
What is the role of telomeres in nonhomologous end joining?
Mark the natural ends of chromosomes
What happens during nonhomologous end joining in humans?
DNA ligase joins the two ends together
What are the 2 ways in which mutagens can cause mutations?
- Base analogs = mutagenic chemicals that look like bases and are incorporated into the DNA
- Direct structural change = DNA is physically changed by environmental factor
What are deaminating agents?
Remove the NH2 group
Change the structures of some nucleotides
What are intercalating agents?
Inserted between base pairs
What is mismatch repair?
Corrects errors in DNA replication
Parent strand contains correct nucleotide
Daughter strand contains the mismatch
