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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

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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Autores principales: Winkelbeiner, Nicola, Wandt, Viktoria K., Ebert, Franziska, Lossow, Kristina, Bankoglu, Ezgi E., Martin, Maximilian, Mangerich, Aswin, Stopper, Helga, Bornhorst, Julia, Kipp, Anna P., Schwerdtle, Tanja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555950/
https://www.ncbi.nlm.nih.gov/pubmed/32917005
http://dx.doi.org/10.3390/ijms21186600
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author Winkelbeiner, Nicola
Wandt, Viktoria K.
Ebert, Franziska
Lossow, Kristina
Bankoglu, Ezgi E.
Martin, Maximilian
Mangerich, Aswin
Stopper, Helga
Bornhorst, Julia
Kipp, Anna P.
Schwerdtle, Tanja
author_facet Winkelbeiner, Nicola
Wandt, Viktoria K.
Ebert, Franziska
Lossow, Kristina
Bankoglu, Ezgi E.
Martin, Maximilian
Mangerich, Aswin
Stopper, Helga
Bornhorst, Julia
Kipp, Anna P.
Schwerdtle, Tanja
author_sort Winkelbeiner, Nicola
collection PubMed
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.
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spelling pubmed-75559502020-10-19 A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice: Impact of Sex and Age Winkelbeiner, Nicola Wandt, Viktoria K. Ebert, Franziska Lossow, Kristina Bankoglu, Ezgi E. Martin, Maximilian Mangerich, Aswin Stopper, Helga Bornhorst, Julia Kipp, Anna P. Schwerdtle, Tanja Int J Mol Sci Article 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. MDPI 2020-09-09 /pmc/articles/PMC7555950/ /pubmed/32917005 http://dx.doi.org/10.3390/ijms21186600 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Winkelbeiner, Nicola
Wandt, Viktoria K.
Ebert, Franziska
Lossow, Kristina
Bankoglu, Ezgi E.
Martin, Maximilian
Mangerich, Aswin
Stopper, Helga
Bornhorst, Julia
Kipp, Anna P.
Schwerdtle, Tanja
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 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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555950/
https://www.ncbi.nlm.nih.gov/pubmed/32917005
http://dx.doi.org/10.3390/ijms21186600
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