MB - DNA Repair Flashcards
What are some examples of spontaneous and induced causes of DNA damage?
Spontaneous
- Replication errors
- Tautomeric shifts
- Deamination
- Depurination
Induced
- Intercalating agents
- Base analogues
- Deaminating agents
- Alkylating agents
- Oxidising agents
- Radiation, U/V
Replication errors
Normal replication introduces the wrong base once every 10^-7 bp, even with proofreading
→Good chance it will get repaired
Repair systems reduce error rate to 10^-10
Some repetitive regions cause slippage of the growing strand insertion of more repeats
→ Can’t be repaired
Tautomeric Shifts
A single chemical compound tends to exist in two or more interconvertible structures
Shifted (enol) form binds G instead of A
Deamination
Loss of base amino group
- C –> U (Pairs A)
- A –> Inosine (Pairs C)
- G –> Xanthine (Pairs C)
Can be repaired
5-Methyl-C –> T (Can’t be repaired)
Depurination
Cleavage of base-sugar bond
- Forms an abasic site (apurinic)
Only occurs to purines (A or G)
What is the Ames test?
Bacterial assay for mutagenesis that helps identify mutagenic agents
Intercalating agents
Insert themselves between bases
- E.g. Ethidium Bromide
FRAMESHIFT MUTATIONS
Base analogues
Chemical which resembles a nucleotide base
- E.g bromouracil (T-analogue)
Incorporated into DNA
More prone to tautomeric shifts
Alkylating agents
Add alkyl groups to nucleobases
e.g.
- Nitrosamines
- Methyl bromide (former grain fumigant)
Deaminating agents
Remove amino groups
e.g.
- Nitrous acid (HNO2)
- Nitrosamines
- Nitrite, Nitrate
Quicker than spontaneous deamination
Oxidising agents
Removes electrons from the structure (Forms C=O bonds)
e.g.
- Superoxide ion (O2-)
- H2O2
Cause of most mutations
Many possible nucleotide alterations
U/V light
UV-induced formation of dimers between adjacent thymines
Radiation
Break Bonds and Create Free Radicals
—>
Single or Double-Strand breaks
Bases chemically altered, linked or detached
