Hypermutation in stationary-phase E-coli: tales from the lac operon

Escherichia coli cells are capable of complex regulatory responses to envir onmental conditions and stresses. In some circumstances, the response inclu des an increase in the mutation rate, effectively mutagenizing the genome. The classic example is the SOS response to DNA damage. Recent work indicate s that other environmental stresses can also result in mutation of the geno me. Modulation of mutation rate may be a more prevalent stress response tha n previously thought. In this review we focus on genome-wide mutation in E. coli cells subjected to a nonlethal genetic selection for reversion of a l ac frameshift allele. Reversion of the lac frameshift allele occurs via a n ovel mechanism that requires homologous recombination functions, and is enh anced by transiently diminished postsynthesis mismatch repair. A model for recombination-dependent stationary-phase mutation will be presented and its relevance for genome-wide mutation discussed.