The Helicobacter pylori MutS protein confers protection from oxidative DNA damage.
The human gastric pathogenic bacterium Helicobacter pylori lacks a MutSLH-like DNA mismatch repair system. Here, we have investigated the functional roles of a mutS homologue found in H. pylori, and show that it plays an important physiological role in repairing oxidative DNA damage. H. pylori mutS mutants are more sensitive than wild-type cells to oxidative stress induced by agents such as H2O2, paraquat or oxygen. Exposure of mutS cells to oxidative stress results in a significant ( approximately 10-fold) elevation of mutagenesis. Strikingly, most mutations in mutS cells under oxidative stress condition are G:C to T:A transversions, a signature of 8-oxoguanine (8-oxoG). Purified H. pylori MutS protein binds with a high specific affinity to double-stranded DNA (dsDNA) containing 8-oxoG as well as to DNA Holliday junction structures, but only weakly to dsDNA containing a G:A mismatch. Under oxidative stress conditions, mutS cells accumulate higher levels (approximately threefold) of 8-oxoG DNA lesions than wild-type cells. Finally, we observe that mutS mutant cells have reduced colonization capacity in comparison to wild-type cells in a mouse infection model.
Wang
Ge
G
Department of Microbiology, University of Georgia, Athens, GA 30602, USA.
Alamuri
Praveen
P
Humayun
M Zafri
MZ
Taylor
Diane E
DE
Maier
Robert J
RJ
D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics / Q000502:physiology*; D016254:Mutagenesis, Insertional; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D010100:Oxygen / Q000633:toxicity; D010269:Paraquat / Q000633:toxicity; D011485:Protein Binding
D016877:Oxidants; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D006861:Hydrogen Peroxide; D051719:MutS DNA Mismatch-Binding Protein; D010269:Paraquat; D010100:Oxygen