Autoren:	Musheev, Michael U. Schomacher, Lars Basu, Amitava Han, Dandan Krebs, Laura Scholz, Carola Niehrs, Christof
Titel:	Mammalian N1-adenosine PARylation is a reversible DNA modification
Online-Publikationsdatum:	12-Apr-2023
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/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.
DDC-Sachgruppe:	570 Biowissenschaften 570 Life sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 10 Biologie
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8832
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Nature Communications 13
Seitenzahl oder Artikelnummer:	6138
Verlag:	Nature Publishing Group
Verlagsort:	London
Erscheinungsdatum:	2022
ISSN:	2041-1723
DOI der Originalveröffentlichung:	10.1038/s41467-022-33731-w
Enthalten in den Sammlungen:	DFG-491381577-G