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bioRxiv · 10.1101/2022.08.17.504244

Mammalian N1-adenosine PARylation is a reversible DNA modification

Musheev, M. U.·Schomacher, L.·Basu, A.·Han, D.·Krebs, L.·Scholz, C.·Niehrs, C.
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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-ribosyl-deoxyinosine to occur in vivo. We conclude that N1-adenosine PARylation is a novel, reversible DNA modification.

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Musheev, M. U., Schomacher, L., Basu, A., Han, D., Krebs, L., Scholz, C., Niehrs, C.. 2022-08-17. Mammalian N1-adenosine PARylation is a reversible DNA modification. https://doi.org/10.1101/2022.08.17.504244

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