내용요약(Abstract)
H2O2 kills E. coli via radicals formed on DNA-bound Fe2+. Killing, mutagenesis, prophage induction and filamentation are greater in μM than lower mM H2O2. In μM H2O2 strand cleavage occurs at dT in RTGR(R=A,G), a promoter motif required for responses of many prokaryotic and eukaryotic genes to iron or oxygen stress. Fe2+interacts rapidly and reversibly with the GN7, allowing first-order oxidation by H2O2 of the Fe2+or DNA-bound radical to quench DNA damage. InmM H2O2 cleavage occurs 5' to a dG in RGGG, a sequence present in telomere repeats. Fe2+ bound to AGGG interacts with two adjacent GN7’ s with localized distortion of the structures on that the rate-limiting step in radical formation is the rearrangement of the structure to allow exposure of the Fe2+ to a single H2O2 molecule to produce a DNA-damaging radical. Above ca. 15mM H2O2 killing is only partially due to DNA damage. In vivo NADH directly or indirectly regenerates Fe2+fromFe3+. E. coli responds to H2O2 exposure by increasing its NADPH:NADH ratio by 6- or 92-fold in 0.5 or5 mM H2O2, respectively. The 2’-phosphate group of NADPH sequesters Fe3+, removing it from closeproximity to the redox-active nicotinamide ring. In eukaryotes NADH is depleted indirectly by polymerization of NAD+to poly(ADP)ribose.