LSM1401 Summary 11 © Lim Fang Jeng
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DNA Damage, Repair and Mutation
RNA and other biomolecules can be replaced but NOT DNA!
- Cells need to repair missing, altered or incorrect bases, bulges of DNA due to insertion/deletion, UV- induced pyrimidine dimers, strand breaks or crosslinks
- Eg: Benzopyrene from tobacco can block between DNA bases, causes hydrogen bond unable to form
After DNA replication (Prokaryotes)
- Mismatch repair system scan DNA duplexes for mismatched bases
o Excise the mispaired region and replace - Methyl-directed pathway to identify which is the
correct strand
- Methylation occurs in post-replication o Methylated strand as parent strand o Remove mismatched bases and replace - MutH, MutS and MutL will bind to the region
nearest to the metylation
- Exonuclease I will remove the DNA regions (3’5’) – ALWAYS see the WRONGLY paired strand
- DNA Pol III fills with correct bases - DNA ligase seals the nicks
Damaged of DNA due to UV-light or Chemical
- Excision repair: Replacement of chemically damaged or modifies bases in DNA - Can be repaired by photolyase
(1) Base excision repair
a. Acts on single base that have been damaged through oxidation or other chemical modification during normal cellular processes
(2) Nucleotide excision repair
a. Recognize larger regions of damaged DNA Actions Examples
- UV irradiation: causes dimerization of adjacent thymine bases disrupting base-pairing - Photolysase will bind at the dimer and uses light to break the bond (repairing the DNA)
- Chemical: Oxygen radicals, in the presence of metal ions, it can destroy sugar rings in DNA by breaking the strand
Base-Excision Repair
- Damaged base excised from sugar-phosphate backbone by DNA glycosylase, create apurinuc/apyrimidic (AP) site
- AP endonuclease to melt the strand
- Exicsion nuclease remove a few bases from AP site - DNA Pol I and DNA ligase ligate the gap
LSM1401 Summary 11 © Lim Fang Jeng
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Nucleotide-Excision Repair
- During serious lesion (excess base) is detected, ABC excinuclease binds to the region
- Cuts out a large piece of DNA
- DNA pol I resynthesize and DNA ligase resealing
Types of Mutation
- Insertion – inserting of one extra base - Deletion – delete of one base
- Nonsense – mutation in which a STOP codon is introduced
- Silent mutation – Mutation that causes no effect (due to third base degeneracy)
Recognition
Removal
Replacement
