This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Iraqui, I. Articles by Huang, M.-E. PubMed PubMed Citation Articles by Iraqui, I. Articles by Huang, M.-E.

Human Peroxiredoxin PrxI Is an Orthologue of Yeast Tsa1, Capable of Suppressing Genome Instability in Saccharomyces cerevisiae

¹ UMR2027 Centre National de la Recherche Scientifique, Institut Curie, Centre Universitaire, Orsay, France and ² Ludwig Institute for Cancer Research, Department of Medicine and Cellular and Molecular Medicine, San Diego School of Medicine, University of California, La Jolla, California

Requests for reprints: Meng-Er Huang, UMR2027 Centre National de la Recherche Scientifique/Institut Curie, Bâtiment 110, Centre Universitaire, 91405 Orsay, France. Phone: 33-1-69863016; Fax: 33-1-69869429; E-mail: meng-er.huang{at}curie.u-psud.fr.

Key Words: peroxiredoxin • oxidative stress • genome instability • S. cerevisiae

The peroxiredoxins (Prx) are conserved antioxidant proteins that use cysteine as the primary site of oxidation during the reduction of peroxides. Many organisms have more than one isoform of Prx. Deletion of TSA1, one of five Prxs in yeast Saccharomyces cerevisiae, results in accumulation of a broad spectrum of mutations including gross chromosomal rearrangements. Deletion of TSA1 is synthetically lethal with mutations in RAD6 and several key genes involved in DNA double-strand break repair. Here, we have examined the function of human PrxI and PrxII, which share a high degree of sequence identity with Tsa1, by expressing them in S. cerevisiae cells under the control of the native TSA1 promoter. We found that expression of PrxI, but not PrxII, was capable of complementing a tsa1 mutant for a variety of defects including genome instability, the synthetic lethality observed in rad6 tsa1 and rad51 tsa1 double mutants, and mutagen sensitivity. Moreover, expression of either Tsa1 or PrxI prevented Bax-induced cell death. These data indicate that PrxI is an orthologue of Tsa1. PrxI and Tsa1 seem to act on the same substrates in vivo and share similar mechanisms of function. The observation that PrxI is involved in suppressing genome instability and protecting against cell death potentially provides a better understanding of the consequences of PrxI dysfunction in human cells. The S. cerevisiae system described here could provide a sensitive tool to uncover the mechanisms that underlie the function of human Prxs. [Cancer Res 2008;68(4):1055–63]