Nicola Lisa Winkelbeiner, Viktoria Klara Veronika Wandt, Franziska Ebert, Kristina Lossow, Ezgi E. Bankoglu, Maximilian Martin, Aswin Mangerich, Helga Stopper, Julia Bornhorst, Anna Patricia Kipp, Tanja Schwerdtle
- 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 damageInvestigation 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.…
MetadatenAuthor details: | Nicola Lisa WinkelbeinerORCiDGND, Viktoria Klara Veronika WandtORCiD, Franziska EbertORCiDGND, Kristina LossowORCiDGND, Ezgi E. Bankoglu, Maximilian Martin, Aswin MangerichORCiDGND, Helga StopperORCiD, Julia BornhorstORCiDGND, Anna Patricia KippORCiDGND, Tanja SchwerdtleORCiDGND |
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DOI: | https://doi.org/10.3390/ijms21186600 |
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ISSN: | 1422-0067 |
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Title of parent work (English): | International Journal of Molecular Sciences |
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Subtitle (English): | Impact of Sex and Age |
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Publisher: | Molecular Diversity Preservation International |
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Place of publishing: | Basel |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2020/09/09 |
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Publication year: | 2020 |
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Release date: | 2020/12/01 |
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Tag: | DNA damage; DNA damage response; ageing; base excision repair (incision activity); liver; maintenance of genomic integrity; poly(ADP-ribosyl)ation; sex |
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Volume: | 21 |
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Issue: | 18 |
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Number of pages: | 19 |
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Funding institution: | Universität Potsdam |
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Funding number: | PA 2020_099 |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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| 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Grantor: | Publikationsfonds der Universität Potsdam |
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Publishing method: | Open Access / Gold Open-Access |
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License (German): | CC-BY - Namensnennung 4.0 International |
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External remark: | Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1021 |
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External remark: | This article is part of this cumulative dissertation. |
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