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 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.

Citation: Sci Rep 7(1) : 216

Date Published: 1st Dec 2017

Registered Mode: Not specified

Authors: Nima Borhan Fakouri, Jon Ambæk Durhuus, Christine Elisabeth Regnell, Maria Angleys, Claus Desler, Md Mahdi Hasan-Olive, Ana Martín-Pardillos, Anastasia Tsaalbi-Shtylik, Kirsten Thomsen, Martin Lauritzen, Vilhelm A. Bohr, Niels de Wind, Linda Hildegard Bergersen, Lene Juel Rasmussen

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Fakouri, N. B., Durhuus, J. A., Regnell, C. E., Angleys, M., Desler, C., Hasan-Olive, M. M., Martín-Pardillos, A., Tsaalbi-Shtylik, A., Thomsen, K., Lauritzen, M., Bohr, V. A., de Wind, N., Bergersen, L. H., & Rasmussen, L. J. (2017). Rev1 contributes to proper mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis. In Scientific Reports (Vol. 7, Issue 1). Springer Science and Business Media LLC.

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Created: 22nd Jan 2019 at 15:07

Last updated: 22nd Jan 2019 at 15:08

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