Gutenberg Open Science: Mammalian N1-adenosine PARylation is a reversible DNA modification

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8832

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DC Field	Value	Language
dc.contributor.author	Musheev, Michael U.	-
dc.contributor.author	Schomacher, Lars	-
dc.contributor.author	Basu, Amitava	-
dc.contributor.author	Han, Dandan	-
dc.contributor.author	Krebs, Laura	-
dc.contributor.author	Scholz, Carola	-
dc.contributor.author	Niehrs, Christof	-
dc.date.accessioned	2023-04-12T07:05:47Z	-
dc.date.available	2023-04-12T07:05:47Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8848	-
dc.description.abstract	Poly-ADP-ribosylation (PARylation) is regarded as a protein-specific modification. However, some PARPs were recently shown to modify DNA termini in vitro. Here, we use ultrasensitive mass spectrometry (LC-MS/MS), anti-PAR antibodies, and anti-PAR reagents to show that mammalian DNA is physiologically PARylated and to different levels in primary tissues. Inhibition of PAR glycohydrolase (PARG) increases DNA PARylation, supporting that the modification is reversible. DNA PARylation requires PARP1 and in vitro PARP1 PARylates single-stranded DNA, while PARG reverts the modification. DNA PARylation occurs at the N1-position of adenosine residues to form N1-Poly(ADP-ribosyl)-deoxyadenosine. Through partial hydrolysis of mammalian gDNA we identify PAR-DNA via the diagnostic deamination product N1-ribosyldeoxyinosine to occur in vivo. The discovery of N1-adenosine PARylation as a DNA modification establishes the conceptual and methodological framework to elucidate its biological relevance and extends the role of PARP enzymes.	en_GB
dc.description.sponsorship	Deutsche Forschungsgemeinschaft (DFG)\|491381577\|Open-Access-Publikationskosten 2022–2024 Universität Mainz - Universitätsmedizin	-
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.title	Mammalian N1-adenosine PARylation is a reversible DNA modification	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8832	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 10 Biologie	de
jgu.organisation.number	7970	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Nature Communications	de
jgu.journal.volume	13	de
jgu.pages.alternative	6138	de
jgu.publisher.year	2022	-
jgu.publisher.name	Nature Publishing Group	de
jgu.publisher.place	London	de
jgu.publisher.issn	2041-1723	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.publisher.doi	10.1038/s41467-022-33731-w	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

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