ADP-Ribosylation of Cytidine: A Novel Nucleic Acid Modification Reversed by NADAR Hydrolases

Mikolčević, Petra; Hloušek-Kasun, Andrea; Schuller, Marion; Lu, Yang; Pirović, Elena; Ahel, Ivan; Mikoč, Andreja (2026) ADP-Ribosylation of Cytidine: A Novel Nucleic Acid Modification Reversed by NADAR Hydrolases. Toxins, 18 (2). ISSN 2072-6651

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Official URL: http://doi.org/10.3390/toxins18020082

Abstract

ADP-ribosylation of nucleic acids is a modification found in both eukaryotes and bacteria, where it contributes to genome maintenance but can also serve as a toxic mechanism used by bacterial toxins to disrupt essential cellular processes. This modification is catalysed by ADP-ribosyltransferases and can be reversed by antagonistic ADP-ribosylgylcohydrolase enzymes. To date, ADP-ribosylation of nucleic acid bases has been described only for adenosine, guanosine, and thymidine. Here we report the ADP-ribosylation of cytidine, catalysed by members of the pierisin family of bacterial toxins—ScARP (SCO5461) and Scabin. We also show that ADP-ribosylation of cytidine is reversible through removal by certain NADAR family proteins, including NADAR proteins from the bacterium Streptomyces coelicolor (SCO5665) and the sponge Amphimedon queenslandica, as well as YbiA-type NADAR proteins. The conservation of cytidine de-ADP-ribosylating activity of NADAR proteins across phylogenetically distant species suggests that this modification may have important physiological significance.

Item Type:

Article

Uncontrolled Keywords:

ADP-ribosylation; cytidine; ScARP/SCO5461; NADAR; SCO5665; Streptomyces

Subjects:

NATURAL SCIENCES

Divisions:

Division of Molecular Biology

Projects: