Mutagens contribute to the human burden of heritable birth defects and cancer and probably to heart disease as well. Most mutagens in most organisms act by triggering a process called error-prone repair (EPR). Such mutagens' primary action is to damage DNA in ways that block the progress of the DNA replication complex. EPR then facilitates damage bypass in a poorly templated (and therefore mutagenic) manner. The bacteriophage T4 uvsX gene plays a central role in EPR and also in recombination. Its product is a recombinase, a protein that catalyzes homologous strand exchange between DNA molecules. The specific role of this protein in EPR remains mysterious. Two analyses are underway. First, although several severe mutations of uvsX are only semilethal, there are hints that an even more drastic disruption of uvsX may be fully lethal. Therefore, host-suppressible mutations will be introduced into several of the early codons of the gene and the resulting mutants will be tested for viability under nonsuppressing conditions. Where the mutants are inviable, the cause of death will be sought by analysing DNA metabolism. Second, a correlation between recombination and mutagenesis will be sought: in a cross employing outside markers, newly induced mutations will be screened for locally enhanced frequencies of recombination.
