Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae

Peroxiredoxins (Prxs) constitute a family of thiol-specific peroxidases that utilize cysteine (Cys) as the primary site of oxidation during the reduction of peroxides. To gain more insight into the physiological role of the five Prxs in budding yeast Saccharomyces cerevisiae, we performed a comparat...

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Autores principales: Iraqui, Ismail, Kienda, Guy, Soeur, Jérémie, Faye, Gérard, Baldacci, Giuseppe, Kolodner, Richard D., Huang, Meng-Er
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688748/
https://www.ncbi.nlm.nih.gov/pubmed/19543365
http://dx.doi.org/10.1371/journal.pgen.1000524
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author Iraqui, Ismail
Kienda, Guy
Soeur, Jérémie
Faye, Gérard
Baldacci, Giuseppe
Kolodner, Richard D.
Huang, Meng-Er
author_facet Iraqui, Ismail
Kienda, Guy
Soeur, Jérémie
Faye, Gérard
Baldacci, Giuseppe
Kolodner, Richard D.
Huang, Meng-Er
author_sort Iraqui, Ismail
collection PubMed
description Peroxiredoxins (Prxs) constitute a family of thiol-specific peroxidases that utilize cysteine (Cys) as the primary site of oxidation during the reduction of peroxides. To gain more insight into the physiological role of the five Prxs in budding yeast Saccharomyces cerevisiae, we performed a comparative study and found that Tsa1 was distinguished from the other Prxs in that by itself it played a key role in maintaining genome stability and in sustaining aerobic viability of rad51 mutants that are deficient in recombinational repair. Tsa2 and Dot5 played minor but distinct roles in suppressing the accumulation of mutations in cooperation with Tsa1. Tsa2 was capable of largely complementing the absence of Tsa1 when expressed under the control of the Tsa1 promoter. The presence of peroxidatic cysteine (Cys(47)) was essential for Tsa1 activity, while Tsa1(C170S) lacking the resolving Cys was partially functional. In the absence of Tsa1 activity (tsa1 or tsa1(CCS) lacking the peroxidatic and resolving Cys) and recombinational repair (rad51), dying cells displayed irregular cell size/shape, abnormal cell cycle progression, and significant increase of phosphatidylserine externalization, an early marker of apoptosis-like cell death. The tsa1(CCS) rad51– or tsa1 rad51–induced cell death did not depend on the caspase Yca1 and Ste20 kinase, while the absence of the checkpoint protein Rad9 accelerated the cell death processes. These results indicate that the peroxiredoxin Tsa1, in cooperation with appropriate DNA repair and checkpoint mechanisms, acts to protect S. cerevisiae cells against toxic levels of DNA damage that occur during aerobic growth.
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spelling pubmed-26887482009-06-19 Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae Iraqui, Ismail Kienda, Guy Soeur, Jérémie Faye, Gérard Baldacci, Giuseppe Kolodner, Richard D. Huang, Meng-Er PLoS Genet Research Article Peroxiredoxins (Prxs) constitute a family of thiol-specific peroxidases that utilize cysteine (Cys) as the primary site of oxidation during the reduction of peroxides. To gain more insight into the physiological role of the five Prxs in budding yeast Saccharomyces cerevisiae, we performed a comparative study and found that Tsa1 was distinguished from the other Prxs in that by itself it played a key role in maintaining genome stability and in sustaining aerobic viability of rad51 mutants that are deficient in recombinational repair. Tsa2 and Dot5 played minor but distinct roles in suppressing the accumulation of mutations in cooperation with Tsa1. Tsa2 was capable of largely complementing the absence of Tsa1 when expressed under the control of the Tsa1 promoter. The presence of peroxidatic cysteine (Cys(47)) was essential for Tsa1 activity, while Tsa1(C170S) lacking the resolving Cys was partially functional. In the absence of Tsa1 activity (tsa1 or tsa1(CCS) lacking the peroxidatic and resolving Cys) and recombinational repair (rad51), dying cells displayed irregular cell size/shape, abnormal cell cycle progression, and significant increase of phosphatidylserine externalization, an early marker of apoptosis-like cell death. The tsa1(CCS) rad51– or tsa1 rad51–induced cell death did not depend on the caspase Yca1 and Ste20 kinase, while the absence of the checkpoint protein Rad9 accelerated the cell death processes. These results indicate that the peroxiredoxin Tsa1, in cooperation with appropriate DNA repair and checkpoint mechanisms, acts to protect S. cerevisiae cells against toxic levels of DNA damage that occur during aerobic growth. Public Library of Science 2009-06-19 /pmc/articles/PMC2688748/ /pubmed/19543365 http://dx.doi.org/10.1371/journal.pgen.1000524 Text en Iraqui et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Iraqui, Ismail
Kienda, Guy
Soeur, Jérémie
Faye, Gérard
Baldacci, Giuseppe
Kolodner, Richard D.
Huang, Meng-Er
Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae
title Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae
title_full Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae
title_fullStr Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae
title_full_unstemmed Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae
title_short Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae
title_sort peroxiredoxin tsa1 is the key peroxidase suppressing genome instability and protecting against cell death in saccharomyces cerevisiae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688748/
https://www.ncbi.nlm.nih.gov/pubmed/19543365
http://dx.doi.org/10.1371/journal.pgen.1000524
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