MECHANISMS OF MUTATION IN BACTERIOPHAGE T4

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Phage T4 growing in Escherichia coli is a powerful model system for the analysis of mechanisms and the genetic control of mutagenesis. Current work centers on two projects. (1) T4 elaborates most of the enzymes required for its own DNA metabolism and is usually indifferent to the functional state of the corresponding host genes. Host mutator mutations define genes that normally reduce mutation rates. Because host mutators have rarely been tested for their effects on T4, we are surveying them using sensitive T4 reversion assays. (2) Heat and low pH promote spontaneous mutational processes in nonreplicating T4 DNA. One of these produces GC-to-TA transversions via modification of dG residues in DNA. Heated dGMP produces many derivatives. We are developing systems to assay the mutagenic dG derivative(s) genetically, and then to produce sufficient amounts to characterize chemically.