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| Cancer Res. Feb (2008); 68(4):1055-63 | |
| Human peroxiredoxin PrxI is an orthologue of yeast Tsa1, capable of suppressing genome instability in Saccharomyces cerevisiae- | |
| Iraqui I, Faye G, Ragu S, Masurel-Heneman A, Kolodner RD, Huang ME | |
| UMR2027 Centre National de la Recherche Scientifique, Institut Curie, Centre Universitaire, Orsay, France- | |
| Abstract: 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- | |
| [PUBMED: 18281480] |   |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |