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The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA

DOI: 10.1016/j.molcel.2016.11.014 DOI Help

Authors: Gytis Jankevicius (University of Oxford) , Antonio Ariza (University of Oxford) , Marijan Ahel (Rudjer Boskovic Institute) , Ivan Ahel (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 64 , PAGES 1109 - 1116

State: Published (Approved)
Published: December 2016
Diamond Proposal Number(s): 9306 , 12346

Open Access Open Access

Abstract: The discovery and study of toxin-antitoxin (TA) systems helps us advance our understanding of the strategies prokaryotes employ to regulate cellular processes related to the general stress response, such as defense against phages, growth control, biofilm formation, persistence, and programmed cell death. Here we identify and characterize a TA system found in various bacteria, including the global pathogen Mycobacterium tuberculosis. The toxin of the system (DarT) is a domain of unknown function (DUF) 4433, and the antitoxin (DarG) a macrodomain protein. We demonstrate that DarT is an enzyme that specifically modifies thymidines on single-stranded DNA in a sequence-specific manner by a nucleotide-type modification called ADP-ribosylation. We also show that this modification can be removed by DarG. Our results provide an example of reversible DNA ADP-ribosylation, and we anticipate potential therapeutic benefits by targeting this enzyme-enzyme TA system in bacterial pathogens such as M. tuberculosis.

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Documents:
1-s2.0-S1097276516307225-main.pdf