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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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.
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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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