The Helicobacter pylori MutS protein confers protection from oxidative DNA damage

Speaker：葉駿達                         Commentator：吳俊忠老師

Date：2005/11/16  14:10~15:00             Place：Room 601

Abstract：

DNA mismatch repair (MMR) system plays a central role in maintaining genetic stability. The best characterized Escherichia coli MMR system consists of three proteins: MutS, MutL, and MutH. Helicobacter pylori, one of the most common gastrointestinal pathogens, has a mutS homologue which belongs to the MutS2 family of proteins but lacks homologues of mutH or mutL gene based on the genome sequence analysis. The absence of a complete set of genes required for an “E. coli like” MMR pathway may indicate that H. pylori lacks a functional MMR system (1). However, it has been shown that Thermus thermophilus MutS2 protein has an endonuclease activity and suggests that H. pylori MutS protein may have both DNA damage repair and incision functions (2). The authors examined if the H. pylori mutS homologue took part in DNA damage repair. They found that if themutS gene of H. pylori had been disrupted, the organism would become more sensitive to oxidative stress, and have higher mutation rate and 8-oxoguanine (8-oxoG) level. They also observed that H. pylori MutS is able to bind to dsDNA containing 8-oxoG with an affinity much higher than that for the G:A or G:T mispair. This suggests that H. pylori MutS may recognize anomalous DNA structure containing 8-oxoG rather than the mismatch sites as observed in conventional MMR. The authors had also noticed that mutS mutant exhibited a decreased efficiency in mouse colonization. These results suggest that MutS protein may play an important role in the oxidative DNA damage repair in H. pylori and may also contribute to the survival of this organism in the host (3).

References：

(1) Simala-Grant, J.L., Lam, E., Keelan, M., Taylor, D.E. (2004) Characterization of the DNA adenine 5'-GATC-3' methylase HpyIIIM from Helicobacter pylori. Curr Microbiol 49: 47–54

(2) Fukui, K., Masui, R., Kuramitsu, S. (2004) Thermus thermophilus MutS2, a MutS paralogue, possesses an endonuclease activity promoted by MutL. J Biochem (Tokyo) 135: 375–384.

(3) Storz, G., Zheng, M. (2000) Oxidative stress. In Bacterial Stress Responses. Storz, G., Hengge-Aronis, R., eds. Washington, DC: ASM Press, pp. 47–60.