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.
| Schultz Jr, Gary E; Drake, John W (2008) Templated mutagenesis in bacteriophage T4 involving imperfect direct or indirect sequence repeats. Genetics 178:661-73 |
| Schultz Jr, Gary E; Carver, Geraldine T; Drake, John W (2006) A role for replication repair in the genesis of templated mutations. J Mol Biol 358:963-73 |
| Kadyrov, Farid A; Drake, John W (2004) UvsX recombinase and Dda helicase rescue stalled bacteriophage T4 DNA replication forks in vitro. J Biol Chem 279:35735-40 |
| Kadyrov, Farid A; Drake, John W (2003) Properties of bacteriophage T4 proteins deficient in replication repair. J Biol Chem 278:25247-55 |
| Kadyrov, Farid A; Drake, John W (2002) Characterization of DNA synthesis catalyzed by bacteriophage T4 replication complexes reconstituted on synthetic circular substrates. Nucleic Acids Res 30:4387-97 |
| Kadyrov, F A; Drake, J W (2001) Conditional coupling of leading-strand and lagging-strand DNA synthesis at bacteriophage T4 replication forks. J Biol Chem 276:29559-66 |
