Previous studies showed that a Bacillus subtilis strain deficient in mismatch repair (MMR; encoded by the mutSL operon) promoted the production of stationary-phase-induced mutations. However, overexpression of the mutSL operon did not completely suppress this process, suggesting that additional DNA repair mechanisms are involved in the generation of stationary-phase-associated mutants in this bacterium. In agreement with this hypothesis, the results presented in this work revealed that starved B. subtilis cells lacking a functional error prevention GO (8-oxo-G) system (composed of YtkD, MutM, and YfhQ) had a dramatic propensity to increase the number of stationary-phase-induced revertants. These results strongly suggest that the occurrence of mutations is exacerbated by reactive oxygen species in nondividing cells of B. subtilis having an inactive GO system. Interestingly, overexpression of the MMR system significantly diminished the accumulation of mutations in cells deficient in the GO repair system during stationary phase. These results suggest that the MMR system plays a general role in correcting base mispairing induced by oxidative stress during stationary phase. Thus, the absence or depression of both the MMR and GO systems contributes to the production of stationary-phase mutants in B. subtilis. In conclusion, our results support the idea that oxidative stress is a mechanism that generates genetic diversity in starved cells of B. subtilis, promoting stationaryphase-induced mutagenesis in this soil microorganism.Adaptive or stationary-phase mutagenesis can be defined as those mutations that permit organisms to grow and divide in response to natural or artificial selection (5) and that occur in nondividing cells during prolonged nonlethal selective pressure, e.g., starvation for an essential amino acid (32). Although this type of mutagenesis was first described in Escherichia coli (7), additional examples of adaptive mutagenesis in other prokaryotes (21, 41) and in eukaryotic organisms (14) have been published. In some cases, these mutations occurred in the absence of specific selection but in response to starvation (11). Regardless of the organisms utilized and the name used, these types of mutations and the processes that generate them are of real interest with respect to evolution and the generation of diversity across all domains of life.Studies with the FЈ lac frameshift reversion construct of E. coli (32) have demonstrated that the generation of Lac ϩ stationary-phase-associated revertants required functional recombination (15), as well as component(s) of the SOS system (24, 25). Further evidence suggests that the mutations generated by this lac system during stationary phase may also be the result of amplification of the plasmid-borne gene followed by SOS-induced mutagenesis and selection (18,38). Recent studies have demonstrated that DNA double-strand-break repair, in addition to the SOS DNA damage response and the error-prone DNA polymerase, are necessary for stress-induced reversion of the E. col...
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