Suppression of the effects of the lack of RpoS by overexpression of SOD or catalase indicated that the damage caused by ROS reduces survival and increases the mutation frequency in a starving P. putida RpoS-deficient strain. Interestingly, although the absence of RpoS in starved P.

putida affected the spectrum of mutations, the spectrum was different from that identified in P. putida lacking the GO repair system (Saumaa et al., 2007). Thus, it is possible that the accumulation of oxidative DNA damage other than GO could elevate the frequency of mutation in these bacteria. There is also another, not exclusive explanation for these differences. It is known that oxidative damage of proteins and membrane components, but not that of selleckchem DNA, is a major reason for mortality of cells (Nyström, 2004). Oxidative damage to components of protein synthesis selleck products increases mistranslation, and

vice versa, mistranslated proteins are more susceptible to oxidative damage (Dukan et al., 2000). Mistranslation is increased 10–100-fold in E. coli due to amino acid starvation (Sørensen, 2001). Importantly, mistranslation of DNA repair and replication proteins has been demonstrated to create a transient mutator phenotype (Humayun, 1998; Balashov & Humayun, 2002, 2003; Al Mamun et al., 2006). For example, hypermutagenesis in E. coli mutA cells mistranslating aspartate as glycine due to a mutation in the glycine tRNA anticodon was mediated by modifications of DNA polymerase Pol III due to elevated mistranslation (Al Mamun et al., 2006). Additionally, oxidative modification of replication proteins and inactivation of the components of repair pathways have been reported in eukaryotic systems (Graziewicz et al., 2002; Men et al., 2007; Montaner et al., 2007; Bae et al., 2008; Jarrett et al., 2008). Hence, because the elevated mutation frequency Flavopiridol (Alvocidib) observed by Tarassova et al. (2009) in starving RpoS-deficient

P. putida was associated with an increased death of bacteria and the spectrum of mutations did not resemble that induced by oxidative damage of DNA, the higher mutation frequency in the surviving populations observed in this study might primarily be caused by a decline in DNA replication and repair fidelity due to the oxidative damage of enzymes and/or the errors occurring during the translation of proteins. So far, the role of oxidative damage to proteins in DNA integrity has been underestimated in stationary-phase mutagenesis. It certainly needs more comprehensive investigations. Bacteria have multiple DNA polymerases, each of those with a specific role. DNA polymerase Pol III is a replicative polymerase, and its inactivation is lethal to bacteria. Pol I is involved in Okazaki fragments’ processing and DNA repair synthesis (Okazaki et al., 1971; Cooper & Hanawalt, 1972). Additionally, E.