Replication Repair

Environmental Health Sciences

Investigators

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Abstract

Summary of Work: DNA damage produces cell death or mutation, both of which can have serious health consequences. 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 fourth but poorly characterized mechanism has been 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 do not otherwise severely affect phage reproduction. The process appears not to involve any of the classical mechanisms and has been named ?replication repair? because it involves enzymes of DNA replication. We have set up the Nossal bacteriophage T4 multi-protein system for replicating both strands of DNA in vitro and we are now investigating the processing of damaged DNA, comparing wild-type and mutant enzymes. (The DNA damage consists of a single, specifically located thymine-thymine dimer.) A mutant DNA-binding protein exhibits reduced affinity for single-stranded DNA, while a mutant replicative DNA helicase exhibits diminished helicase activity.