Replication Repair

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Unrepaired DNA damage can result in cell death or mutation, either of which can have serious health consequences. The classically defined mechanisms of DNA repair are direct reversal of the damage, excision of the damage followed by resynthesis of the damaged strand, a cut-and-paste recombinational process that bypasses the damage without removing it, and mutagenic translesion synthesis. A new recombination-like mechanism called ?replication repair? was postulated many years ago and was characterized recently in bacteriophage T4 using both genetic and enzymological methods. Two parallel pathways seem to operate, one employing the T4 SSB and replicative helicase and the other the T4 recombinase and a different helicase. In each pathway, a blocked primer terminus switches to the other daughter strand, uses it briefly as a template, and then switches back to the cognate parental strand having bypassed the DNA damage. This template-switching mechanism avoids the mutations that might otherwise arise during translesion synthesis. However, there is a minor class of mutations that often generates multiple mutations in a single event, mutations that are associated with various kinds of repeated sequences and that seem to be templated. Like replication repair, these mutations are modeled as the products of template switching, but the ectopic template can be the other parental strand in the neighborhood of an imperfect reverse repeat (a quasipalindrome). We are therefore investigating whether mutations that impair replication repair also affect templated mutagenesis.