SSB + BER1 Flashcards
Single stranded breaks and base excision repair 1 (23 cards)
What are the 4 different types of base damage?
- Substitution
- Alkylation - adding a methyl group
- Loss - losing a base due to natural hydrolysis
- Oxidation - via peroxides
What are the 2 different types of sugar damage?
- Hydrogen abstraction
- Oxidation
What is deamination and when does it happen?
- Loss an amino group
- Happens during base substitution
What is the product of the deamination of 5-methyl cytosine?
Thymine
What is the product of the deamination of Adenine?
Hypoxanthine
What is the product of the deamination of Cytosine?
Uracil
What is the product of the deamination of Guanine?
Xanthine
Which 4 bases are similar to each-other in base substitution?
- Thymine is similar to uracil
- Guanine is similar to hypoxanthine
Explain the term ‘pre-mutagenic’
- When there is DNA damage, it needs to be recognised
- If the cell goes into S phase before the damage is recognised, it is read as NORMAL
- This is pre-mutagenic, which can be fixed before the next cell cycle.
What is a point mutation?
When the cell does not fix the pre-mutagenic base and it continues onto the next cell cycle as if it is not there.
Which bases are pyrimidines?
Thymine and Cytosine
Which bases are purines?
Guanine and Adenine
What is a transverse mutation?
Purine –> Pyrimidine
Pyrimidine –> Purine
What is a transition mutation?
Purine –> Purine
Pyrimidine –> Pyrimidine
What are the 3 most common positions of base alkylation?
- N7MG
- O6MG
- N3MA
What is monofunctional alkylation?
When damage is caused in one nucleophilic centre in DNA.
Describe spontaneous alkylation
- When S-Adenosyl Methionine (SAM) forms O6MG
- O6MG looks like Adenine
- Therefore it mismatches with Thymine
- This is a transition mutation
What is induced alkylation caused by?
Caused by carcinogens found in:
- Tobacco
- Overcooked meat
- Car Exhaust fumes
Describe spontaneous base loss
- Caused by the hydrolysis of the N-Glycosyl bond between the sugar and the base
- Causing depurination and depyrimidation
What is induced base loss caused by?
Environmental alkylation agents such as:
- Aflatoxin
- BPDE
What is spontaneous base oxidation caused by?
Cellular metabolites such as ROS.
What is induced base oxidation caused by?
- X-Rays
- Cosmic radiation
- Radon
Give an example of a base oxidation scenario
- Guanine + Oxidation = 8 Hydroxy-Guanine (8HG)
- 8HG is similar to Thymine, therefore Adenine is paired with it = Pre- Mutagenic
- Another round of replication occurs forming T:A T:A base pairs because it thinks the 8HG is a Thymine so it keeps replicating Thymine.
- The 8HG is completely missed = Mutation.