DNA damage can be repaired

All organisms have developed the means to repair damage to their DNA, in addition to the proofreading mechanism described earlier

The most common way of dealing with mutations is by means of a method called excision repair, in which enzymes recognise and cut out the altered region of DNA and then fill in the missing bases, using the other strand as a template (Figure 11.22). Mismatch repair is used to repair the incorporation of a base that has escaped the proofreading system. In a situation such as this, it is not immediately obvious which is the correct base and which is the mistake, so how does the cell know which strand to replace? In E. coli, the old strand is distinguished from the new by the fact that some of its bases are methylated. This only occurs some time after replication, so newly synthesised strands will not have the methyl groups and can thus be recognised.

Less frequently, the alteration in DNA structure is simply reversed by direct repair mechanisms, the best known of which is photoreactivation. This involves an enzyme

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Mutation

Nicks made in phosphate-sugar backbone either side of mutation

Affected section removed

New strand synthesised with correct sequence

Figure 11.22 Excision repair. A section of the affected strand either side of the mutation is removed and replaced by the action of DNA polymerase and DNA ligase called DNA photolyase, which breaks the bonds formed between adjacent thymine bases by UV light (see above) before replication takes place. Unusually, the photolyase is dependant on visible light (>300nm) for activation. Another form of direct repair, involving the enzyme methylguanine transferase allows the reversal of the effects of alkylating agents.

Loss of repair mechanisms can allow mutations to become established which would normally be corrected. A harmful strain of E. coli which emerged in the 1980s was shown to have developed its pathogenicity due to a deficiency in its repair enzymes.

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