TARG1 protects against toxic DNA ADP-ribosylation.
Nucleic Acids Res
; 49(18): 10477-10492, 2021 10 11.
Article
em En
| MEDLINE
| ID: mdl-34508355
ABSTRACT
ADP-ribosylation is a modification that targets a variety of macromolecules and regulates a diverse array of important cellular processes. ADP-ribosylation is catalysed by ADP-ribosyltransferases and reversed by ADP-ribosylhydrolases. Recently, an ADP-ribosyltransferase toxin termed 'DarT' from bacteria, which is distantly related to human PARPs, was shown to modify thymidine in single-stranded DNA in a sequence specific manner. The antitoxin of DarT is the macrodomain containing ADP-ribosylhydrolase DarG, which shares striking structural homology with the human ADP-ribosylhydrolase TARG1. Here, we show that TARG1, like DarG, can reverse thymidine-linked DNA ADP-ribosylation. We find that TARG1-deficient human cells are extremely sensitive to DNA ADP-ribosylation. Furthermore, we also demonstrate the first detection of reversible ADP-ribosylation on genomic DNA in vivo from human cells. Collectively, our results elucidate the impact of DNA ADP-ribosylation in human cells and provides a molecular toolkit for future studies into this largely unknown facet of ADP-ribosylation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tioléster Hidrolases
/
DNA
/
Adenosina Difosfato Ribose
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article