Figure 7. Stress-Response Models for Adaptive Amplification and Point Mutation.

Modified from Lombardo et al. (2004) and Rosenberg and Hastings (2004a). DSBR, DSB repair; hypermutation, increased mutation at lac and elsewhere. The origins of DSEs during starvation on lactose medium in this assay system are unknown, and possibilities are reviewed elsewhere (Rosenberg 2001). On the F′ plasmid carrying the lac gene, DSEs may be frequent and may be derived from chronic single-strand nicks at the origin of transfer. However chromosomal mutation during starvation on lactose medium in these cells also requires DSB repair proteins (Bull et al. 2001), and so probably results from (lower levels of) DSEs generated in the chromosome, independently of the transfer origin, or perhaps by transient integration of the F′ into the chromosome (Hfr formation). Both adaptive point mutation and amplification are proposed to be outcomes of RpoS-dependent stress response, which both mechanisms require (Lombardo et al. 2004), and to result from alternative error-prone ways of repairing DSBs.