DNA repair and Maintenance of Genome Stability Flashcards
What is a transition mutation?
Pyrimidine to Pyrimidine
T->C
What is a transversion mutation?
Pyrimidine to purine
T->G
Types of pyrimidine
Cytosine
Thymine
Types of purines
Adenine
Guanine
What can induce DNA damage
UV light
Give an example of when can mutations be advantageous?
When the cells only survive in arginine, they can mutate so that you can live without arginine present
What is a nucleotide?
A bass + sugar + phosphate backbone
what can point mutations cause?
stop codons
silent mutations
point mutations - effects gene function
How is DNA read?
triplet codons
What are the consequences of mutations?
Gene amplification Broken genes Fused genes Altered genes Missing code Damaged gene
What causes mutations?
Luck Inherited predisposition Environmental: External e.g. smoking Internal e.g. free the metabolised oxygen which attack the DNA
Know the types of DNA damage
Nucleotide damage (UV light) e.g. pyrimidine dimer
Abasic site (hydrolysis)
Base damage:
- Cytosine deamination e.g. uracil
- Alkylating agents e.g. 06 methyl adenine
- Reactive oxygen e.g. oxoguanine
cause does depurination cause?
spontaneous reaction with water
what is the consequence of depurination?
base loss
What causes mutations?
Replication, a base change does not cause the mutation, it is the replication with the base change
What causes deamination?
Spontaneous, specialist deaminases
What is the result of deamination?
Mismatch
What is the reactive species equation?
Oxygen -> Superoxide -> Hydrogen peroxide -> Hydroxyl radical
Name the reactive oxygen species which are dangerous
Superoxide
Hydrogen peroxide
Hydroxyl radical
Peroxisomes
What produces reactive oxygen species?
Mitochondria
What is the consequence of reactive oxygen species?
Base mispair
Consequences of UV light?
Mispair
What does UV form?
covalent bonds between adjacent bases between pyrimidine
What is the result of reactions with alkalyting agents?
loss of base, misread during replication
what is the conequences of bulky adducts?
non-coding base
Why does bulkby adducts cause mutations?
body tries to excrete chemicals, cytochrome p450 tries to let you pee them out, makes it more reactive and it is the derivatives of the chemicals which attack your DNA
What does alcohol cause?
chemicals which interact with both strands of the DNA meaning you cannot pull them apart `
Why do mutations happen all of the time?
There is not enough genes in the body to encode for all of the functions of the immune system so these genes are segmented because it is confident that it is able to repair them
Explain proofreading
DNA polymerase adds the wrong nucleotide, it recognises them and goes back to remove them and then able to extend it
What is the DNA repair pathway for mis-matched bases?
Mismatch repair
What is the DNA repair pathway for base damage?
Base excision repair
What is the DNA repair pathway for nucleotide damage?
Nucleotide excision repair
What is the DNA repair pathway for DNA breaks?
Non-homologous end joining
Microhomology mediated joining
Homologous recombination
Describe mismatch repair in eukaryotes
There is a nick in the newly synthesised strand
Protein (MSH) binds to the nick and causes it to form a loop
The newly synthesised strand is digested
Insertion of nucleotides to fix the strand
Describe mismatch repair in prokaryotes
There is a nick in the newly synthesised strand
The old strand is methylated so the protein knows which one the old one is
Protein (MutS) binds to the nick and causes it to form a loop
The newly synthesised strand is digested
Insertion of nucleotides to fix the strand
Describe base excision repair
The base is removed by glycosylase
Sugar phosphate is removed by AP endonuclease and drp lyase
Gap is filled by polymerase and DNA ligase
Describe nucleotide excision repair
Pyrimidine dimer - DNA damage recognise
Helicase unwinds the DNA around damage and nucleases cut section of damaged strand 5’ and 3’ to damage
DNA polymerase and ligase
Describe non-homologous end joining
‘clean break’, ends held together by Ku70/80
DNA ligase joins ends
why is non-homologous end joining error prone?
there can be a dirty break and this results in loss of base pairs - deletion mutation
Describe microhomology end joining
'dirty', non-ligatable ends DNA ends resect to produce single strand DNA Complimentary DNA strands revealed Pairing of complimentary ends Ligated by DNA ligase
Describe homologous recombination
Sister chromatids CtIP DNA ends resected to generate single strand DNA RAD51 Homology search and strand invasion DNA synthesis and branch migration 'Missing' information replaced DNA ligation
Example of a DNA repair signature
scars
