Replication Repair

Environmental Health Sciences

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Abstract

Summary of Work: Unrepaired DNA damage produces cell death or mutation, either of which can have serious health consequences. In most organisms, most DNA damage is repaired before it can cause harm. The classically defined mechanisms of DNA repair are direct reversal of the damage, excision of the damage followed by resynthesis of the damaged strand, recombinational processes that bypass the damage without removing it, and mutagenic translesion synthesis. A poorly characterized mechanism was identified in bacteriophage T4. Mutations in certain genes of DNA replication reduce survival after treatments inducing a variety of kinds of DNA damage, but the mutations hardly affect phage reproduction. The process does not involve any of the classical mechanisms and was named "replication repair" because it involves enzymes of DNA replication. We set up a bacteriophage T4 eight-protein system for replicating both strands of DNA in vitro using an artificial replication fork. We reported previously that DNA damage could be bypassed in this system by a mechanism based on template switching (from one parental strand to the other daughter strand) in a process driven the T4 protein that binds single-stranded DNA (gp32) and the T4 replicative helicase (gp41). We now find that the same reaction can be driven even more efficiently by the T4 recombinase (UvsX) plus another T4 helicase called Dda.