DNA Replication: Repair Mechanisms
Introduction
- Most cells have only one or two sets of genomic DNA
- Damaged protein and RNA → Replaceable, by using info encoded in DNA
- But DNA → Irreplaceable
- So... maintaining the integrity of the info in DNA is vital, which is supported by complex set of DNA repair systems.
- DNA can be damaged by many processes, some are spontaneous and others caused by environmental agents.
- Replication can occasionally damage info in DNA, when errors introduce mismatched base pairs (e.g. G with T)
- The chemistry of DNA damage → very diverse and complex!
- Cellular response to this damage includes wide range of enzymatic systems that cause chemical transformations in DNA metabolism!
DNA replicated with high fidelity (accuracy/less errors)
- Mis-pairing occurs 1 in 10^8-10^10 base pairs
- High replication accury arises because:
- Mis-pairing occurs 1 in 10^8-10^10 base pairs
- High replication accury arises because:
- Cells maintain balanced levels of dNTPs, reducing chances of mis-incorporation
- Polymerase exhibits a open (inactive) and closed (active) form which helps to properly position an incoming nucleotide.
- 3' to 5' exonuclease activity of DNA polymerase detects and eliminates the occasional errors.
- Addition DNA repair systems exist:
- Action of DNA polymerase I, DNA photolyase, DNA glycosylate
- Mismatch repair system
- Base excision repair
- Nucleotide excision repair system
Chemical Mutagens (Nitrous acid, dimethy sulphate, acridine orange)
- Mutations fall into 2 major categories
- Transitions - purine (or pyrimidine) replaced by another purine (or pyrimidine)
- Transversion - purine replaced by a pyrimidine (or vice versa)