A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age
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 o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6600 |
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| 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 |
| author_facet | 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 |
| author_sort | Nicola Winkelbeiner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:27:29Z |
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| id | doaj.art-785fca78a8db46e5b6217912c2f67c2c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:27:29Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-785fca78a8db46e5b6217912c2f67c2c2023-11-20T13:07:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118660010.3390/ijms21186600A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and AgeNicola Winkelbeiner0Viktoria K. Wandt1Franziska Ebert2Kristina Lossow3Ezgi E. Bankoglu4Maximilian Martin5Aswin Mangerich6Helga Stopper7Julia Bornhorst8Anna P. Kipp9Tanja Schwerdtle10Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyDepartment of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyDepartment of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyTraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), 14558 Berlin-Potsdam-Jena-Wuppertal, GermanyInstitute of Pharmacology and Toxicology, University of Würzburg, Versbacher Straße 9, 97078 Würzburg, GermanyDepartment of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyDepartment of Biology, Molecular Toxicology Group, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, GermanyInstitute of Pharmacology and Toxicology, University of Würzburg, Versbacher Straße 9, 97078 Würzburg, GermanyTraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), 14558 Berlin-Potsdam-Jena-Wuppertal, GermanyTraceAge—DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), 14558 Berlin-Potsdam-Jena-Wuppertal, GermanyDepartment of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyInvestigation 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.https://www.mdpi.com/1422-0067/21/18/6600maintenance of genomic integrityageingsexDNA damagebase excision repair (incision activity)DNA damage response |
| spellingShingle | 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 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 maintenance of genomic integrity ageing sex DNA damage base excision repair (incision activity) DNA damage response |
| title | A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age |
| title_full | A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age |
| title_fullStr | A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age |
| title_full_unstemmed | A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age |
| title_short | A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age |
| title_sort | multi endpoint approach to base excision repair incision activity augmented by parylation and dna damage levels in mice impact of sex and age |
| topic | maintenance of genomic integrity ageing sex DNA damage base excision repair (incision activity) DNA damage response |
| url | https://www.mdpi.com/1422-0067/21/18/6600 |
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