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

## TL;DR

Scientists discovered a new type of nucleic acid modification involving cytidine, which can be reversed by specific enzymes across different species.

## Contribution

The study identifies ADP-ribosylation of cytidine as a novel modification and shows its reversal by NADAR hydrolases.

## Key findings

- ADP-ribosylation of cytidine is catalyzed by pierisin family toxins like ScARP and Scabin.
- NADAR proteins from diverse species can reverse cytidine ADP-ribosylation.
- The conservation of this activity suggests physiological importance of the modification.

## 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.