5M3I

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

(2016) Mol Cell 64: 1109-1116

• PubMed: 27939941 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1016/j.molcel.2016.11.014
• Primary Citation of Related Structures:  
  5M31, 5M3E, 5M3I


• PubMed 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.

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Organizational Affiliation: 

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE Oxford, UK.