Tromans-Coia, Callum and Sanchi, Andrea and Moeller, Giuliana K. and Timinszky, Gyula and Lopes, Massimo (2021) TARG1 protects against toxic DNA ADP-ribosylation. NUCLEIC ACIDS RESEARCH, 49 (18). pp. 10477-10492. ISSN 0305-1048
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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.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Wellcome TrustWellcome TrustEuropean Commission [101794, 210634]; Biotechnology and Biological Sciences Research CouncilUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC) [BB/R007195/1]; Ovarian Cancer Research Alliance (Collaborative Research Development) [813369]; Cancer Research United KingdomCancer Research UK [C35050/A22284]; Swiss National Science Foundation (SNF)Swiss National Science Foundation (SNSF) [310030 189206]; Hungarian Academy of SciencesHungarian Academy of Sciences [LP201711/2017]; National Research Development and Innovation OfficeNational Research, Development & Innovation Office (NRDIO) - Hungary [K128239] Funding text: The Ivan Ahel Laboratory is supported by the Wellcome Trust [101794, 210634]; Biotechnology and Biological Sciences Research Council [BB/R007195/1]; Ovarian Cancer Research Alliance (Collaborative Research Development) [813369]; Cancer Research United Kingdom [C35050/A22284]; Work in the Lopes lab has been supported by the Swiss National Science Foundation (SNF) [310030 189206]; the Timinszky laboratory is supported by the Hungarian Academy of Sciences [LP201711/2017]; National Research Development and Innovation Office [K128239]. Funding for open access charge: Wellcome Trust. |
| Uncontrolled Keywords: | MECHANISM; DAMAGE; REPAIR; poly(ADP-ribose); denileukin diftitox; CHOLERA-TOXIN; Homologous recombination; LETHAL FACTOR; PIERISIN-1; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 07 Feb 2022 11:06 |
| Last Modified: | 07 Feb 2022 11:06 |
| URI: | http://real.mtak.hu/id/eprint/137478 |
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