Schuller, M., Raggiaschi, R., Mikolcevic, P. et al. (7 more authors) (2023) Molecular basis for the reversible ADP-ribosylation of guanosine bases. Molecular Cell, 83 (13). E6. pp. 2303-2315. ISSN 1097-2765
Abstract
Modification of nucleic acids by ADP-ribosylation is catalyzed by various ADP-ribosyltransferases, including the DarT enzyme. The latter is part of the bacterial toxin-antitoxin (TA) system DarTG, which was shown to provide control of DNA replication and bacterial growth as well as protection against bacteriophages. Two subfamilies have been identified, DarTG1 and DarTG2, which are distinguished by their associated antitoxins. While DarTG2 catalyzes reversible ADP-ribosylation of thymidine bases employing a macrodomain as antitoxin, the DNA ADP-ribosylation activity of DarTG1 and the biochemical function of its antitoxin, a NADAR domain, are as yet unknown. Using structural and biochemical approaches, we show that DarT1-NADAR is a TA system for reversible ADP-ribosylation of guanosine bases. DarT1 evolved the ability to link ADP-ribose to the guanine amino group, which is specifically hydrolyzed by NADAR. We show that guanine de-ADP-ribosylation is also conserved among eukaryotic and non-DarT-associated NADAR members, indicating a wide distribution of reversible guanine modifications beyond DarTG systems.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | ADP-ribosylation; ADP-ribosyltransferases; PARPDNA damage; toxin-antitoxin system; DNA modifications |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Jul 2023 15:35 |
Last Modified: | 04 Oct 2024 11:10 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.molcel.2023.06.013 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201216 |
Downloads
Filename: 1-s2.0-S1097276523004574-main.pdf
Licence: CC-BY 4.0
Filename: mmc1.pdf
Licence: CC-BY 4.0