Mutagens contribute to the human burden of heritable birth defects and cancer and probable to heart disease as well. Most of the mutagenic and lethal effects of DNA-damaging agents are prevented by DNA repair systems. The classically described systems repair damage before DNA replication (by direct reversal or by excision repair), at the replication fork (by mutagenic bypass of damaged bases) or after replication (by a recombinational process). We have recently described a new mode of repair operating in bacteriophage T4. It is defined by several mutations that enhance killing by DNA-damaging agents. These mutations reside in vital genes encoding enzymes of DNA replication, and repair appears to occur during replication itself. The repair system is accurate (nonmutagenic). To date, mutations defective in replication repair have been found in the genes encoding the DNA helicase and the SSB protein (which binds single-stranded DNA, holding it in an extended configuration suitable for DNA replication). Attempts are underway to find further mutations affecting this repair process by screening the genes encoding T4 DNA primase and DNA polymerase.
