SummaryEnvironmental and physiological stress conditions can transiently alter the fidelity of DNA replication. The DNA damage-mediated SOS response in Escherichia coli is the best-known example of such an 'inducible mutagenesis' or 'transient mutator' pathway. Emerging evidence suggests the existence of a number of other stress-inducible pathways that also affect the fidelity of replication. Among the more provocative recent findings are UVM, an SOS-independent damageinducible mutagenic pathway, and a new recA-dependent but umuD/C-independent pathway that appears to be provoked by translational stress. These findings alter our view of inducible mutagenesis, and anticipate the existence of previously unrecognized links between protein synthesis and DNA replication.
The SOS hypothesisThe idea of inducible error-prone replication evolved from observations such as enhanced mutagenesis of UV-irradiated lambda phage in UV-irradiated cells compared with unirradiated cells. A unifying mechanism that tightly links base insertion opposite a DNA lesion and lesion bypass, as proposed by the SOS hypothesis, is both logical and simple. Experimental evidence supporting elements of the SOS hypothesis came from a large number of laboratories, and the hypothesis in turn provided the theoretical framework for rapid advances in the identification and characterization of the SOS regulon (for review see Friedberg et al., 1995). According to current interpretation, unrepaired bulky or non-instructive DNA damage blocks DNA replication and can be lethal unless specific proteins are induced to stimulate DNA repair and to restore replication past blocked sites. The expression of these proteins is normally repressed by the binding of the LexA protein to the promoter. An SOS-inducing signal is generated when DNA replication is arrested at sites of damage. It is believed that aborted replication exposes single-stranded DNA at replication forks to binding by the RecA protein. The DNA-bound RecA protein undergoes a conformational transition to RecA * , the SOS-active form of the RecA protein.