Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses

The DNA damage response revolves around transmission of information via post-translational modifications, including reversible protein ADP-ribosylation. Here, we applied a mass-spectrometry-based Af1521 enrichment technology for the identification and quantification of ADP-ribosylation sites as a fu...

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Autores principales:	Sara C. Buch-Larsen, Alexandra K. L. F. S. Rebak, Ivo A. Hendriks, Michael L. Nielsen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ADP-ribosylation PARP DNA damage Af1521 post-translational modification proteomics Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8aa9a7a9161441cdaf3987627d1fdd60
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spelling	oai:doaj.org-article:8aa9a7a9161441cdaf3987627d1fdd602021-11-25T17:09:03ZTemporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses10.3390/cells101129272073-4409https://doaj.org/article/8aa9a7a9161441cdaf3987627d1fdd602021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2927https://doaj.org/toc/2073-4409The DNA damage response revolves around transmission of information via post-translational modifications, including reversible protein ADP-ribosylation. Here, we applied a mass-spectrometry-based Af1521 enrichment technology for the identification and quantification of ADP-ribosylation sites as a function of various DNA damage stimuli and time. In total, we detected 1681 ADP-ribosylation sites residing on 716 proteins in U2OS cells and determined their temporal dynamics after exposure to the genotoxins H<sub>2</sub>O<sub>2</sub> and MMS. Intriguingly, we observed a widespread but low-abundance serine ADP-ribosylation response at the earliest time point, with later time points centered on increased modification of the same sites. This suggests that early serine ADP-ribosylation events may serve as a platform for an integrated signal response. While treatment with H<sub>2</sub>O<sub>2</sub> and MMS induced homogenous ADP-ribosylation responses, we observed temporal differences in the ADP-ribosylation site abundances. Exposure to MMS-induced alkylating stress induced the strongest ADP-ribosylome response after 30 min, prominently modifying proteins involved in RNA processing, whereas in response to H<sub>2</sub>O<sub>2</sub>-induced oxidative stress ADP-ribosylation peaked after 60 min, mainly modifying proteins involved in DNA damage pathways. Collectively, the dynamic ADP-ribosylome presented here provides a valuable insight into the temporal cellular regulation of ADP-ribosylation in response to DNA damage.Sara C. Buch-LarsenAlexandra K. L. F. S. RebakIvo A. HendriksMichael L. NielsenMDPI AGarticleADP-ribosylationPARPDNA damageAf1521post-translational modificationproteomicsBiology (General)QH301-705.5ENCells, Vol 10, Iss 2927, p 2927 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ADP-ribosylation PARP DNA damage Af1521 post-translational modification proteomics Biology (General) QH301-705.5
spellingShingle	ADP-ribosylation PARP DNA damage Af1521 post-translational modification proteomics Biology (General) QH301-705.5 Sara C. Buch-Larsen Alexandra K. L. F. S. Rebak Ivo A. Hendriks Michael L. Nielsen Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses
description	The DNA damage response revolves around transmission of information via post-translational modifications, including reversible protein ADP-ribosylation. Here, we applied a mass-spectrometry-based Af1521 enrichment technology for the identification and quantification of ADP-ribosylation sites as a function of various DNA damage stimuli and time. In total, we detected 1681 ADP-ribosylation sites residing on 716 proteins in U2OS cells and determined their temporal dynamics after exposure to the genotoxins H<sub>2</sub>O<sub>2</sub> and MMS. Intriguingly, we observed a widespread but low-abundance serine ADP-ribosylation response at the earliest time point, with later time points centered on increased modification of the same sites. This suggests that early serine ADP-ribosylation events may serve as a platform for an integrated signal response. While treatment with H<sub>2</sub>O<sub>2</sub> and MMS induced homogenous ADP-ribosylation responses, we observed temporal differences in the ADP-ribosylation site abundances. Exposure to MMS-induced alkylating stress induced the strongest ADP-ribosylome response after 30 min, prominently modifying proteins involved in RNA processing, whereas in response to H<sub>2</sub>O<sub>2</sub>-induced oxidative stress ADP-ribosylation peaked after 60 min, mainly modifying proteins involved in DNA damage pathways. Collectively, the dynamic ADP-ribosylome presented here provides a valuable insight into the temporal cellular regulation of ADP-ribosylation in response to DNA damage.
format	article
author	Sara C. Buch-Larsen Alexandra K. L. F. S. Rebak Ivo A. Hendriks Michael L. Nielsen
author_facet	Sara C. Buch-Larsen Alexandra K. L. F. S. Rebak Ivo A. Hendriks Michael L. Nielsen
author_sort	Sara C. Buch-Larsen
title	Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses
title_short	Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses
title_full	Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses
title_fullStr	Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses
title_full_unstemmed	Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses
title_sort	temporal and site-specific adp-ribosylation dynamics upon different genotoxic stresses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8aa9a7a9161441cdaf3987627d1fdd60
work_keys_str_mv	AT saracbuchlarsen temporalandsitespecificadpribosylationdynamicsupondifferentgenotoxicstresses AT alexandraklfsrebak temporalandsitespecificadpribosylationdynamicsupondifferentgenotoxicstresses AT ivoahendriks temporalandsitespecificadpribosylationdynamicsupondifferentgenotoxicstresses AT michaellnielsen temporalandsitespecificadpribosylationdynamicsupondifferentgenotoxicstresses
_version_	1718412662750052352

Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses

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