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Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis
Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624938/ https://www.ncbi.nlm.nih.gov/pubmed/28970491 http://dx.doi.org/10.1038/s41598-017-12662-3 |
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author | Fakouri, Nima Borhan Durhuus, Jon Ambæk Regnell, Christine Elisabeth Angleys, Maria Desler, Claus Hasan-Olive, Md Mahdi Martín-Pardillos, Ana Tsaalbi-Shtylik, Anastasia Thomsen, Kirsten Lauritzen, Martin Bohr, Vilhelm A. de Wind, Niels Bergersen, Linda Hildegard Rasmussen, Lene Juel |
author_facet | Fakouri, Nima Borhan Durhuus, Jon Ambæk Regnell, Christine Elisabeth Angleys, Maria Desler, Claus Hasan-Olive, Md Mahdi Martín-Pardillos, Ana Tsaalbi-Shtylik, Anastasia Thomsen, Kirsten Lauritzen, Martin Bohr, Vilhelm A. de Wind, Niels Bergersen, Linda Hildegard Rasmussen, Lene Juel |
author_sort | Fakouri, Nima Borhan |
collection | PubMed |
description | Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress. Here, we show that Rev1-deficiency in mouse embryo fibroblasts or mouse liver tissue is associated with replicative stress and mitochondrial dysfunction. In addition, Rev1-deficiency is associated with high poly(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD(+), low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis. |
format | Online Article Text |
id | pubmed-5624938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56249382017-10-12 Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis Fakouri, Nima Borhan Durhuus, Jon Ambæk Regnell, Christine Elisabeth Angleys, Maria Desler, Claus Hasan-Olive, Md Mahdi Martín-Pardillos, Ana Tsaalbi-Shtylik, Anastasia Thomsen, Kirsten Lauritzen, Martin Bohr, Vilhelm A. de Wind, Niels Bergersen, Linda Hildegard Rasmussen, Lene Juel Sci Rep Article Nucleic acids, which constitute the genetic material of all organisms, are continuously exposed to endogenous and exogenous damaging agents, representing a significant challenge to genome stability and genome integrity over the life of a cell or organism. Unrepaired DNA lesions, such as single- and double-stranded DNA breaks (SSBs and DSBs), and single-stranded gaps can block progression of the DNA replication fork, causing replicative stress and/or cell cycle arrest. However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to bypass some DNA lesions, which can circumvent the process leading to replication fork arrest and minimize replicative stress. Here, we show that Rev1-deficiency in mouse embryo fibroblasts or mouse liver tissue is associated with replicative stress and mitochondrial dysfunction. In addition, Rev1-deficiency is associated with high poly(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD(+), low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis. Nature Publishing Group UK 2017-10-02 /pmc/articles/PMC5624938/ /pubmed/28970491 http://dx.doi.org/10.1038/s41598-017-12662-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Fakouri, Nima Borhan Durhuus, Jon Ambæk Regnell, Christine Elisabeth Angleys, Maria Desler, Claus Hasan-Olive, Md Mahdi Martín-Pardillos, Ana Tsaalbi-Shtylik, Anastasia Thomsen, Kirsten Lauritzen, Martin Bohr, Vilhelm A. de Wind, Niels Bergersen, Linda Hildegard Rasmussen, Lene Juel Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis |
title | Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis |
title_full | Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis |
title_fullStr | Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis |
title_full_unstemmed | Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis |
title_short | Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1α axis |
title_sort | rev1 contributes to proper mitochondrial function via the parp-nad(+)-sirt1-pgc1α axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624938/ https://www.ncbi.nlm.nih.gov/pubmed/28970491 http://dx.doi.org/10.1038/s41598-017-12662-3 |
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