The proposed experiments are intended to provide basic information on the relative frequency and specificity of base substitution and frameshift mutational events and, more importantly, to address the question of the mechanisms through which these events are produced at the molecular level. Focus will be on studies with purified replication proteins including DNA polymerases. These will be used to synthesize defined viral DNA probes in vitro which will permit the selection of various mutational events in in vivo biological assays. The exact nature of the mutational events will be determined by DNA sequence analysis.