Lecture 4 Flashcards
What is tautomerisation of bases?
A base flips into a different isomer with different base-pairing properties
This creates mismatch pairs
What are two mechanisms to avoid mutations?
- DNA proofreading
2. Mismatch repair system
Explain DNA proofreading
- DNA polymerase ‘check’s each new base pair
- If there’s a mistake it will back up and remove the wrong base
Explain the Mismatch Repair System
- Can detect non-matched ‘pairs’ of bases in DNA molecules
- Can determine which of the bases is wrong and removes this base
How do these system recognise the incorrect base?
System can recognise what’s ‘original’ (correct) and new (incorrect) strands of the DNA molecule because DNA inside E.Coli is chemically modified by METHYLATION
Describe methylation
Chemical modification of bases in the DNA. Process doesn’t affect pairing of bases
What is an indel mutation?
Insertions or deletions of one or more base pairs
What are indel mutations thought to arise from?
Errors during DNA replication
Describe the Streisinger model
DNA ‘slippage’ results in loss/incorporation of new base pair
According to the Streisinger model, what happens to cause an insertion?
NEWLY SYNTHESISED STRAND SLIPS
The extra base loops out, the loops is stabilised by repetitive sequences. On the next round of replication a new base pair is added
According to the Streisinger model, what happens to cause a deletion?
TEMPLATE STRAND SLIPS
The extra base loops out, the loops is stabilised by repetitive sequences. On the next round of replication a base pair is deleted
What is the accuracy of DNA polymerase?
~1 in 10 ^5 mistakes
Following proofreading and mismatch repairs, what is the number of spontaneous mutations?
1 per 10^9 base pairs
This frequency represents the balance between lesions and repairs