Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase
Ribonucleotide reductase (RNR) is an essential holoenzyme required for de novo synthesis of dNTPs. The Saccharomyces cerevisiae genome encodes for two catalytic subunits, Rnr1 and Rnr3. While Rnr1 is required for DNA replication and DNA damage repair, the function(s) of Rnr3 is unknown. Here, we sho...
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| Format: | Article |
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Shared Science Publishers OG
2019-05-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/2019a-corcoles-saez-microbial-cell/ |
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| author | Isaac Corcoles-Saez Jean-Luc Ferat Michael Costanzo Charles M. Boone Rita S. Cha |
| author_facet | Isaac Corcoles-Saez Jean-Luc Ferat Michael Costanzo Charles M. Boone Rita S. Cha |
| author_sort | Isaac Corcoles-Saez |
| collection | DOAJ |
| description | Ribonucleotide reductase (RNR) is an essential holoenzyme required for de novo synthesis of dNTPs. The Saccharomyces cerevisiae genome encodes for two catalytic subunits, Rnr1 and Rnr3. While Rnr1 is required for DNA replication and DNA damage repair, the function(s) of Rnr3 is unknown. Here, we show that carbon source, an essential nutrient, impacts Rnr1 and Rnr3 abundance: Non-fermentable carbon sources or limiting concentrations of glucose down regulate Rnr1 and induce Rnr3 expression. Oppositely, abundant glucose induces Rnr1 expression and down regulates Rnr3. The carbon source dependent regulation of Rnr3 is mediated by Mec1, the budding yeast ATM/ATR checkpoint response kinase. Unexpectedly, this regulation is independent of all currently known components of the Mec1 DNA damage response network, including Rad53, Dun1, and Tel1, implicating a novel Mec1 signalling axis. rnr3D leads to growth defects under respiratory conditions and rescues temperature sensitivity conferred by the absence of Tom6, a component of the mitochondrial TOM (translocase of outer membrane) complex responsible for mitochondrial protein import. Together, these results unveil involvement of Rnr3 in mitochondrial functions and Mec1 in mediating the carbon source dependent regulation of Rnr3. |
| format | Article |
| id | doaj-art-ae93b009a3c14805bceb4ce2e6c9a37f |
| institution | DOAJ |
| issn | 2311-2638 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | Shared Science Publishers OG |
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| series | Microbial Cell |
| spelling | doaj-art-ae93b009a3c14805bceb4ce2e6c9a37f2025-08-20T02:53:21ZengShared Science Publishers OGMicrobial Cell2311-26382019-05-016628629410.15698/mic2019.06.680Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductaseIsaac Corcoles-Saez0Jean-Luc Ferat1Michael Costanzo2Charles M. Boone3Rita S. Cha4School of Medical Sciences, North West Cancer Research Institute, Bangor University, Deniol Road, Bangor, LL57 2UW, United Kingdom.Institute of Integrative Biology of the Cell (I2BC), Avenue de la Terrasse, Paris, France.University of Toronto, Donnelly Centre, 160 College Street, Toronto, Ontario, M5S 3E1, Canada.University of Toronto, Donnelly Centre, 160 College Street, Toronto, Ontario, M5S 3E1, Canada.School of Medical Sciences, North West Cancer Research Institute, Bangor University, Deniol Road, Bangor, LL57 2UW, United Kingdom.Ribonucleotide reductase (RNR) is an essential holoenzyme required for de novo synthesis of dNTPs. The Saccharomyces cerevisiae genome encodes for two catalytic subunits, Rnr1 and Rnr3. While Rnr1 is required for DNA replication and DNA damage repair, the function(s) of Rnr3 is unknown. Here, we show that carbon source, an essential nutrient, impacts Rnr1 and Rnr3 abundance: Non-fermentable carbon sources or limiting concentrations of glucose down regulate Rnr1 and induce Rnr3 expression. Oppositely, abundant glucose induces Rnr1 expression and down regulates Rnr3. The carbon source dependent regulation of Rnr3 is mediated by Mec1, the budding yeast ATM/ATR checkpoint response kinase. Unexpectedly, this regulation is independent of all currently known components of the Mec1 DNA damage response network, including Rad53, Dun1, and Tel1, implicating a novel Mec1 signalling axis. rnr3D leads to growth defects under respiratory conditions and rescues temperature sensitivity conferred by the absence of Tom6, a component of the mitochondrial TOM (translocase of outer membrane) complex responsible for mitochondrial protein import. Together, these results unveil involvement of Rnr3 in mitochondrial functions and Mec1 in mediating the carbon source dependent regulation of Rnr3.http://microbialcell.com/researcharticles/2019a-corcoles-saez-microbial-cell/Rnr1Rnr3Mec1carbon sourcerespirationmitochondriadNTP |
| spellingShingle | Isaac Corcoles-Saez Jean-Luc Ferat Michael Costanzo Charles M. Boone Rita S. Cha Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase Microbial Cell Rnr1 Rnr3 Mec1 carbon source respiration mitochondria dNTP |
| title | Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase |
| title_full | Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase |
| title_fullStr | Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase |
| title_full_unstemmed | Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase |
| title_short | Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase |
| title_sort | functional link between mitochondria and rnr3 the minor catalytic subunit of yeast ribonucleotide reductase |
| topic | Rnr1 Rnr3 Mec1 carbon source respiration mitochondria dNTP |
| url | http://microbialcell.com/researcharticles/2019a-corcoles-saez-microbial-cell/ |
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