MECHANISMS OF MUTATION IN BACTERIOPHAGE T4

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Bacteriophage T4 growing in Escherichia coli is an ancestral model system for studying mutagenesis and DNA repair. Recent work has produced the following results. (1) Heat produces G:C -> T:A transversions via modification of G residues in nonreplicating T4 DNA. The process is highly variable, appears to depend on trace components of the medium, and may involve a spontaneously activated oxygen species. (2) Spontaneous mutation rates in the T4 rII system are largely independent of both temperature and medium. (3) Growth at pH 9 or mutations in the cya or crp genes strongly increases resistance to UV in E. coli, but not in T4. The photoreactivation and excision-repair systems interact in E. coli but not in T4. However, a T4 mutant defective in replication repair appers to be refractory to photoreactivation. (4) Forward mutation in the T4 system is usually scored by counting r mutants, which arise at five genes. Two of these, rI and rV, remain uncharacterized. The rV gene has been mapped and is being sequenced. (5) Phage RB69 is a distant relative of T4. The RB69 DNA polymerase shares only 61.5% amino acid identify with the T4 DNA polymerase but the RB69 gene can complement a defect in the T4 gene. The fidelity of DNA replication in this configuration is close to normal in vivo.