Piecing Together How Peroxiredoxins Maintain Genomic Stability
Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/7/12/177 |
| _version_ | 1797728086946480128 |
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| author | James D. West Trevor J. Roston Joseph B. David Kristin M. Allan Matthew A. Loberg |
| author_facet | James D. West Trevor J. Roston Joseph B. David Kristin M. Allan Matthew A. Loberg |
| author_sort | James D. West |
| collection | DOAJ |
| description | Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker’s yeast (<i>Saccharomyces cerevisiae</i>) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species. |
| first_indexed | 2024-03-12T11:09:45Z |
| format | Article |
| id | doaj.art-a3584b9918b2422aa9bf48dc6f395a6d |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T11:09:45Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-a3584b9918b2422aa9bf48dc6f395a6d2023-09-02T03:14:40ZengMDPI AGAntioxidants2076-39212018-11-0171217710.3390/antiox7120177antiox7120177Piecing Together How Peroxiredoxins Maintain Genomic StabilityJames D. West0Trevor J. Roston1Joseph B. David2Kristin M. Allan3Matthew A. Loberg4Biochemistry & Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, OH 44691, USABiochemistry & Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, OH 44691, USABiochemistry & Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, OH 44691, USABiochemistry & Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, OH 44691, USABiochemistry & Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, OH 44691, USAPeroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker’s yeast (<i>Saccharomyces cerevisiae</i>) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species.https://www.mdpi.com/2076-3921/7/12/177peroxiredoxinoxidative stressthioredoxinthiol peroxidasemutatorgenomic instabilitysulfiredoxinredox switchribonucleotide reductase |
| spellingShingle | James D. West Trevor J. Roston Joseph B. David Kristin M. Allan Matthew A. Loberg Piecing Together How Peroxiredoxins Maintain Genomic Stability Antioxidants peroxiredoxin oxidative stress thioredoxin thiol peroxidase mutator genomic instability sulfiredoxin redox switch ribonucleotide reductase |
| title | Piecing Together How Peroxiredoxins Maintain Genomic Stability |
| title_full | Piecing Together How Peroxiredoxins Maintain Genomic Stability |
| title_fullStr | Piecing Together How Peroxiredoxins Maintain Genomic Stability |
| title_full_unstemmed | Piecing Together How Peroxiredoxins Maintain Genomic Stability |
| title_short | Piecing Together How Peroxiredoxins Maintain Genomic Stability |
| title_sort | piecing together how peroxiredoxins maintain genomic stability |
| topic | peroxiredoxin oxidative stress thioredoxin thiol peroxidase mutator genomic instability sulfiredoxin redox switch ribonucleotide reductase |
| url | https://www.mdpi.com/2076-3921/7/12/177 |
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