Weaver/Molecular Biology

Mismatch Repairs

So far, we have been discussing repair of bulky DNA damage caused by external agents. What about DNA that simply has a mismatch due to incorporation of the wrong base and failure of the proofreading system? At first, it would seem tricky to repair such a mistake, because of the apparent difficulty in determining which strand is the newly synthesized one that has the mistake and which is the parental one that should be left alone. At least in E. coli this is not a problem, because the parental strand has identification tags that distinguish it from the progeny strand. These tags are methylated adenines, created by a methylating enzyme that recognizes the sequence GATC and places a methyl group on the A. Since this four-base sequence occurs approximately every 250 base pairs, there is usually one not far from a newly created mismatch.

Moreover, GATC is a palindrome, so the opposite strand also reads GATC in the 5'® 3' direction. This means that a newly synthesized strand across from a methylated GATC is also destined to become methylated, but a little time elapses before that can happen. The mismatch repair system (Figure 9) takes advantage of this delay; it uses the methylation on the parental strand as a signal to leave that strand alone and correct the nearby mismatch in the unmethylated progeny strand. This process must occur fairly soon after the mismatch is created, or both strands will be methylated and no distinction between them will be possible. Eukaryotic mismatch repair is not as well understood as that in E. coli, but the genes encoding the repair enzymes are very well conserved, so the mechanisms are likely to be similar.

Summary: The E. coli mismatch repair system recognizes the parental strand by its methylated adenines in GATC sequences. Then it corrects the mismatch in the complementary (progeny) strand.

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