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A multi-endpoint approach to base excision repair incision activity augmented by PARylation and DNA damage levels in mice: impact of sex and age
Please always quote using this URN: urn:nbn:de:bvb:20-opus-285706
- 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-radioactiveInvestigation 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.…
Author: | Nicola Winkelbeiner, Viktoria K. Wandt, Franziska Ebert, Kristina Lossow, Ezgi E. Bankoglu, Maximilian Martin, Aswin Mangerich, Helga Stopper, Julia Bornhorst, Anna P. Kipp, Tanja Schwerdtle |
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URN: | urn:nbn:de:bvb:20-opus-285706 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Pharmakologie und Toxikologie |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Year of Completion: | 2020 |
Volume: | 21 |
Issue: | 18 |
Article Number: | 6600 |
Source: | International Journal of Molecular Sciences (2020) 21:18, 6600. https://doi.org/10.3390/ijms21186600 |
DOI: | https://doi.org/10.3390/ijms21186600 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | DNA damage; DNA damage response; ageing; base excision repair (incision activity); liver; maintenance of genomic integrity; poly(ADP-ribosyl)ation; sex |
Release Date: | 2023/06/14 |
Date of first Publication: | 2020/09/09 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |