Direct and inducible mutagenesis in mammalian cells

The understanding of mutagenic mechanisms in mammalian cells is based on extrapolations of results obtained in prokaryotes and simple eukaryotes. The use of animal viruses as targets for mutagenesis suggests that these extrapolations may be valid: recent data indicate that mutagenesis of ultraviolet-damaged templates in mammalian cells seems to occur at similar sites to that observed in prokaryotes; furthermore, nuclear replicating animal viruses are subject to the phenomenon of ultraviolet-enhanced reactivation, called SOS reactivation in bacteria. In experiments analogous to Weigle mutagenesis of phage, several groups have shown that animal cells appear to respond to DNA damage by induction of mutagenic pathways which can act upon infecting viral genomes. Recent experiments with shuttle vectors that can replicate both in animal cells and in bacteria have confirmed these conclusions. These vectors now make possible the rapid recovery of mutant genes for direct sequence analysis.