DNA Damage And Repair Flashcards
What are the 4 types of DNA damage?
1) replication error
2) base tautomers
3) covalent damage
4) non-covalent interaction
What are base tautomers?
Base tautomers are alternative isomeric forms present for a small portion of time
What happens when an Enol group binds to a Thymine?
It’s becomes a base tautomer so it binds with G instead of A which can cause changes to the wrong base.
What is strand slippage?
Slippage is when there are some of the same bases but bind to wrong base causing an excess base to be outside
What is cytosine deamination?
Cytosine is subject to deamination to uracil.
What happens to create an Abasic sugar?
Loss of a base by hydrolysis so there is no base
What happens if guanine is oxidised?
Produces 8-oxo-G which pairs A instead of C leading to changes in pattern
Fact for ya init:
Alfotoxin B produced by peanut mould is activated by P450 in the liver is a reactive species that modifies guanine by mutations
What are intercalating agents?
They are usually aromatic rings that cause frame shift because the new polymerase insets another base
Name an intercalating agent?
Ethidium
Name 4 types of DNA repair?
Direct repair
Base excision repair
Nucleotide excision repair
Mismatch repair
what is direct repair?
Removes damaged bases
What is base excision repair?
Removes damaged base
What is nucleotide excision repair?
Removes damaged nucleotide
What is mismatch repair?
Excision of a long strand containing the mistake
How do flavoproteins repair DNA lesions?
Flavoproteins contain two light harvesting co-factors that in the presence of light release FADH free radicals that act as electron donor to break pyrimidine dimers
What are DNA lesions?
They are thymine dimers caused by UV exposure
How does UvrABC excinuclease removed thymine dimers?
UvrABC excinuclease cuts 8 bases on 5’ side and 4 bases on the 3’ side removing the dimer which is then sealed by Pol 1 and DNA ligase.
How does nucleotide excision repair occur in prokaryotes?
A hetero dimer of 2xUvrA and 1 UvrB detect DNA damage UvrA is repaced by UvrC. UvrBC complex cuts out 8 bases on 5’ and 4bases on 3’. The gap is then filled by polymerase 1 and ligase.
How is nucleotide excision repair done in eukaryotes?
XPC recognise the lesion allowing XPA+XPD to open and bind to DNA. Using RPA to stabilise the open complex. Then ERCC1-XPF and XPG create the incision to remove the oligonucleotide and pol 1 +ligase fill gap
How is the deamination of cytosine to uracil repaired?
Uracil-N-glycosylase cuts the glycosidic bond. Ap ending lease cuts the back bone and pol 1 fills in by nick translation and ligase.
What is the purpose of uracil-N-glycosylase?
To Remove U opposite G but also opposite A.
How does uracil-N-glycosylase discriminate between U and T?
The base is flipped from inside to outside and if it fits like uracil would it would be cleaved.
Wheat happens when there is a change in Keto group of G?
It becomes 8-oxo-G and binds to A instead of C
What is the mechanism for mismatch repair?
MutS binds to the mismatch and mutH binds to DNA which is hemimethylated allowing for distinguishing of daughter and parent strand MutL links H and S. MutH then cuts unmethylated strands DNA segment.
What is the SOS response?
This a response to damaged ssDNA this activates LexA which cleaves itself. In it’s cleaved form LexA increases transcription of repair proteins.
What are the two types of double strand repair?
Homologous and non-homologous
In double strand repair why isn’t it put on the end of chromosomes?
As they have telomeres that signal not to
What is p53 arrest?
A tumour suppressor gene that holds cell cycle at G1/S phase if DNA is damaged. If irreparable can initiate apoptosis. If mutated can lead to cancer.
