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Originally published In Press as doi:10.1074/jbc.M301577200 on March 31, 2003

J. Biol. Chem., Vol. 278, Issue 23, 20708-20715, June 6, 2003
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The YggX Protein of Salmonella enterica Is Involved in Fe(II) Trafficking and Minimizes the DNA Damage Caused by Hydroxyl Radicals

RESIDUE CYS-7 IS ESSENTIAL FOR YggX FUNCTION*

Jeffrey A. Gralnick {ddagger} and Diana M. Downs §

From the Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin 53706

Previous work from our laboratory identified YggX as a protein whose accumulation increased the resistance of Salmonella enterica to superoxide stress, reversed defects attributed to oxidized [Fe-S] clusters, and decreased the spontaneous mutation frequency of the cells. Here we present work aimed at determining why the accumulation of YggX correlates with reduced mutation frequency. Genetic and biochemical data showed that accumulation of YggX reduced the damage to DNA by hydroxyl radicals. The ability of purified YggX to protect DNA from Fenton chemistry mediated damage in vitro and to decrease the concentration of Fe(II) ions in solution available for chelation provided a framework for the interpretation of data obtained from in vivo experiments. The interpretation of in vitro assay results, within the context of the in vivo phenotypes, was validated by a mutant variant of YggX (C7S) that was unable to function in vivo or in vitro. We propose a model, based on data presented here and reported earlier, that suggests YggX is a player in Fe(II) trafficking in bacteria.


Received for publication, February 13, 2003 , and in revised form, March 28, 2003.

* This work was supported in part by National Science Foundation Grant MCB0096513 and National Institutes of Health Grant GM47296. The J. S. McDonnell Foundation also provided funds from a 21st Century Scientist Scholars Award. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} Supported by the Jerome J. Stefaniak Predoctoral Fellowship from the Department of Bacteriology.

§ To whom correspondence should be addressed: Dept. of Bacteriology, 1550 Linden Dr., Madison, WI 53706. Tel.: 608-265-4630; Fax: 608-262-9865; E-mail: downs{at}bact.wisc.edu.


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