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Authors: Musheev, Michael U.
Schomacher, Lars
Basu, Amitava
Han, Dandan
Krebs, Laura
Scholz, Carola
Niehrs, Christof
Title: Mammalian N1-adenosine PARylation is a reversible DNA modification
Online publication date: 12-Apr-2023
Year of first publication: 2022
Language: english
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: 570 Biowissenschaften
570 Life sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 10 Biologie
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: Nature Communications
Pages or article number: 6138
Publisher: Nature Publishing Group
Publisher place: London
Issue date: 2022
ISSN: 2041-1723
Publisher DOI: 10.1038/s41467-022-33731-w
Appears in collections:DFG-491381577-G

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