Cargando…
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...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shared Science Publishers OG
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545439/ https://www.ncbi.nlm.nih.gov/pubmed/31172013 http://dx.doi.org/10.15698/mic2019.06.680 |
_version_ | 1783423384097390592 |
---|---|
author | Corcoles-Saez, Isaac Ferat, Jean-Luc Costanzo, Michael Boone, Charles M. Cha, Rita S. |
author_facet | Corcoles-Saez, Isaac Ferat, Jean-Luc Costanzo, Michael Boone, Charles M. Cha, Rita S. |
author_sort | Corcoles-Saez, Isaac |
collection | PubMed |
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. rnr3Δ 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 | Online Article Text |
id | pubmed-6545439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Shared Science Publishers OG |
record_format | MEDLINE/PubMed |
spelling | pubmed-65454392019-06-06 Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase Corcoles-Saez, Isaac Ferat, Jean-Luc Costanzo, Michael Boone, Charles M. Cha, Rita S. Microb Cell Research Article 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. rnr3Δ 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. Shared Science Publishers OG 2019-05-20 /pmc/articles/PMC6545439/ /pubmed/31172013 http://dx.doi.org/10.15698/mic2019.06.680 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged. |
spellingShingle | Research Article Corcoles-Saez, Isaac Ferat, Jean-Luc Costanzo, Michael Boone, Charles M. Cha, Rita S. Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase |
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 | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545439/ https://www.ncbi.nlm.nih.gov/pubmed/31172013 http://dx.doi.org/10.15698/mic2019.06.680 |
work_keys_str_mv | AT corcolessaezisaac functionallinkbetweenmitochondriaandrnr3theminorcatalyticsubunitofyeastribonucleotidereductase AT feratjeanluc functionallinkbetweenmitochondriaandrnr3theminorcatalyticsubunitofyeastribonucleotidereductase AT costanzomichael functionallinkbetweenmitochondriaandrnr3theminorcatalyticsubunitofyeastribonucleotidereductase AT boonecharlesm functionallinkbetweenmitochondriaandrnr3theminorcatalyticsubunitofyeastribonucleotidereductase AT charitas functionallinkbetweenmitochondriaandrnr3theminorcatalyticsubunitofyeastribonucleotidereductase |