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Article

A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age

1
Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
2
TraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), 14558 Berlin-Potsdam-Jena-Wuppertal, Germany
3
Department of Molecular Nutritional Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 24, 07743 Jena, Germany
4
German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
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Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Straße 9, 97078 Würzburg, Germany
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Department of Biology, Molecular Toxicology Group, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany
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Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, Germany
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German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(18), 6600; https://doi.org/10.3390/ijms21186600
Received: 27 August 2020 / Revised: 7 September 2020 / Accepted: 7 September 2020 / Published: 9 September 2020
(This article belongs to the Section Molecular Biology)
Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery. View Full-Text
Keywords: maintenance of genomic integrity; ageing; sex; DNA damage; base excision repair (incision activity); DNA damage response; poly(ADP-ribosyl)ation; liver maintenance of genomic integrity; ageing; sex; DNA damage; base excision repair (incision activity); DNA damage response; poly(ADP-ribosyl)ation; liver
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MDPI and ACS Style

Winkelbeiner, N.; Wandt, V.K.; Ebert, F.; Lossow, K.; Bankoglu, E.E.; Martin, M.; Mangerich, A.; Stopper, H.; Bornhorst, J.; Kipp, A.P.; Schwerdtle, T. A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age. Int. J. Mol. Sci. 2020, 21, 6600. https://doi.org/10.3390/ijms21186600

AMA Style

Winkelbeiner N, Wandt VK, Ebert F, Lossow K, Bankoglu EE, Martin M, Mangerich A, Stopper H, Bornhorst J, Kipp AP, Schwerdtle T. A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age. International Journal of Molecular Sciences. 2020; 21(18):6600. https://doi.org/10.3390/ijms21186600

Chicago/Turabian Style

Winkelbeiner, Nicola, Viktoria K. Wandt, Franziska Ebert, Kristina Lossow, Ezgi E. Bankoglu, Maximilian Martin, Aswin Mangerich, Helga Stopper, Julia Bornhorst, Anna P. Kipp, and Tanja Schwerdtle. 2020. "A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age" International Journal of Molecular Sciences 21, no. 18: 6600. https://doi.org/10.3390/ijms21186600

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