Oxygen-dependent mutagenesis in Escherichia coli lacking superoxide dismutase.

Abstract

Escherichia coil double mutants (sodA sodB) completely lacking superoxide dismutase (SOD) have greatly enhanced mutation rates during aerobic growth. Single mutants lacking manganese SOD (MnSOD) but possessing iron SOD (FeSOD) have a smaller increase, and single mutants lacking FeSOD but possessing MnSOD do not show such an increase. The enhancement of mutagenesis is completely dependent on the presence of oxygen, and treatments that increase the flux of superoxide radicals produce even higher levels of mutagenesis. The presence of a plasmid overproducing either form of SOD reduces the level of mutagenesis to that of wild type, showing that the 02-dependent enhancement results from a lack of SOD. The enhancement of mutagenesis is RecA-independent, and a complete lack of SOD does not induce the SOS response during aerobic growth. However, the enhanced mutagenesis in aerobically grown sodA sodB mutants is largely dependent on functional exonuclease Ill, suggesting that the increased flux of superoxide radicals results in DNA lesions that can be acted on by this enzyme, leading to mutations.

The superoxide dismutases of Candida glabrata protect against oxidative damage and are required for lysine biosynthesis, DNA integrity and chronological life survival

“…cerevisiae and E. coli SOD mutants are more prone to mutations (Farr et al, 1986;Huang et al, 2003) and contain high levels of intracellular free iron, which is evidenced by their marked Fenton-dependent DNA damage (Srinivasan et al, 2000). Consistent with these observations, we showed that SOD mutants of C. glabrata exhibited not only high levels of O 2 $2 , but also sensitivity to DNA damage agents and a high mutation rate (Fig.…”

“…The protective role of the SODs in Candida glabrata been shown that mutations in SOD genes lead to increased rates of spontaneous mutation in E. coli (Farr et al, 1986) and Sac. cerevisiae (Gralla & Valentine, 1991).…”

Implication of (Mn)superoxide dismutase of Enterococcus faecalis in oxidative stress responses and survival inside macrophages

“…The presence of SODs in virtually all facultative and aerobic organisms and several anaerobes suggests that O N{ 2 presents a problem for organisms growing in the presence of O 2 . Although in vitro experiments have established that O N{ 2 does not react detectably with biomolecules (Imlay, 2002(Imlay, , 2003, characterization of mutants lacking cytosolic SOD has provided the first in vivo evidence that excess O N{ 2 causes DNA damage (Farr et al, 1986;Keyer et al, 1995). Several studies conducted with Escherichia coli have provided strong support for the theory that O N{ 2 triggers the Fenton reaction (H 2 O 2 zFe 2z ?O N{ 2 zFe 3z zOH { ) by the oxidative release of iron from iron-containing molecules, such as those containing [4Fe-4S] clusters, thereby increasing the pool of free iron available to catalyse hydroxyl Abbreviations: Cm, chloramphenicol; DAPE, diaminopimelate epimerase; Em, erythromycin; MnSOD, manganese-containing superoxide dismutase; RACE-PCR, rapid amplification of cDNA ends PCR; ROS, reactive oxygen species; SOD, superoxide dismutase; tBOOH, tertbutylhydroperoxide.…”

Cellular Defenses against Superoxide and Hydrogen Peroxide

“…Both sets of mutants exhibit catabolic and biosynthetic defects that stem from the inactivation of a family of dehydratases (15,16 (17,18). H 2 O 2 directly oxidizes unincorporated intracellular ferrous iron, some of which is associated with DNA (19,20):…”