Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-8832
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 |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-8832 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Nature Communications 13 |
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 |
Files in This Item:
File | Description | Size | Format | ||
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mammalian_n1adenosine_parylat-20230222082913471.pdf | 1.67 MB | Adobe PDF | View/Open |