DNA Repair by Reversal of Damage

Abstract

Some DNA repair mechanisms involve the simple reversal of DNA damage. These processes require a single protein that is able first to recognize DNA damage, and then to catalyse the reversal of damage to the DNA, thus restoring the DNA to its original state.

Keywords: DNA damage; DNA repair; photolyase; O6‐methylguanine DNA repair methyltransferase; photoreactivation

Figure 1.

Chemical structure of specific types of DNA base damage subject to direct reversal. (a) Cyclobutane pyrimidine dimer (CPD) produced by UV light. (b) Pyrimidine (6‐4) pyrimidone photoproduct ((6‐4) photoproduct) produced by UV light. (c) 5‐Thyminyl‐5,6‐dihydrothymine (spore photoproduct) produced specifically in A DNA by UV light. (d) O6MeG produced by methylating agents. (e) O4MeT produced by methylating agents. (f) Potential base pairing of O6MeG with thymine (top) and O4MeT with guanine (bottom).

Figure 2.

The transfer of methyl groups from DNA by DNA repair MTases. O6MeG, O4MeT and MePT (S‐diastereomer only) lesions in double‐stranded DNA are recognized by DNA repair MTases and the inappropriate methyl group is transferred to a cysteine residue in the active site of the MTase protein. Methyl transfer inactivates the MTase and so these DNA repair proteins have been called suicide enzymes.

Figure 3.

The adaptive response to methylating agents. Methyl transfer from a MePT to cysteine‐69 on E. coli Ada turns Ada into a potent transcriptional activator that increases expression from the ada gene as well as from the alkA gene, which encodes the DNA repair enzyme, 3‐methyladenine DNA glycosylase, and two other genes, alkB and aidB, which are also thought to play a role in cellular resistance to alkylating agents.

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References

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Further Reading

Friedberg EC, Walker GC and Siede W (1995) DNA repair by reversal of damage. In: DNA Repair and Mutagenesis, pp. 91–133. Washington, DC: American Society for Microbiology Press.

Lindahl T, Sedgwick B, Sekiguchi M and Nakabeppu Y (1988) Regulation and expression of the adaptive response to alkylating agents. Annual Review of Biochemistry 57: 133–157.

Pieper RO (1998) Cellular responses to methylation damage. In: Nickoloff JA and Hoekstra MF (eds) DNA Damage and Repair: DNA Repair in Higher Eukaryotes, pp. 33–49. Totowa, NJ: Humana Press.

Yasui A and Eker APM (1998) DNA photolyases. In: Nickoloff JA and Hoekstra MF (eds) DNA Damage and Repair: DNA Repair in Higher Eukaryotes, pp. 9–32. Totowa, NJ: Humana Press.

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Memisoglu, Asli, and Samson, Leona D(Apr 2001) DNA Repair by Reversal of Damage. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000579]