Human peroxiredoxin PrxI is an orthologue of yeast Tsa1, capable of suppressing genome instability in Saccharomyces 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 tsa1Delta mutant for a variety of defects including genome instability, the synthetic lethality observed in rad6 Delta tsa1Delta and rad51 Delta tsa1Delta 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.
Iraqui
Ismail
I
UMR2027 Centre National de la Recherche Scientifique, Institut Curie, Centre Universitaire, Orsay, France.
Faye
Gérard
G
Ragu
Sandrine
S
Masurel-Heneman
Amélie
A
Kolodner
Richard D
RD
Huang
Meng-Er
ME
D000595:Amino Acid Sequence; D042822:Genomic Instability; D018398:Homeodomain Proteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010544:Peroxidases / Q000235:genetics*; D054464:Peroxiredoxins / Q000096:biosynthesis / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
D018398:Homeodomain Proteins; C512693:PRRX2 protein, human; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; C515940:PRDX1 protein, human; D054464:Peroxiredoxins