ArticleThe EMBO journal2013
Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.
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Who cites it
201 citing papers in PubMed, 301 citations in OpenAlex.
- NADRSC chemical biology · 2026Review
- Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation.FEBS letters · 2026Article
- Structure, function, regulation, evolution, and therapeutic implications of PARP14.Genes & development · 2026Review
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response.PLoS biology · 2026Article
- Reversible RNA ADP-ribosylation on uracil bases.Nucleic acids research · 2026Article
- Screening assay to monitor mono-ADP-ribosylhydrolase activity of viral macrodomains in cells.Communications biology · 2026Article
- Chemical Synthesis of Native ADP-Ribosylated Oligonucleotides Enables Analysis of DNA ADP-Ribosylation Hydrolase Specificity.Journal of the American Chemical Society · 2026Article
- PARG regulates the proteasomal degradation of TARG1.Cell reports · 2026Article
- Crystal structures and snapshots along Tpt1-catalyzed phosphate transfer from nucleic acid to NADNature communications · 2025Article
- Phenotypic Diversity in Stress-induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures: Novel Associations with Parkinsonism, Icthyosis and Cataract.Cerebellum (London, England) · 2025Article
- Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose.The EMBO journal · 2025Article
- Family-wide analysis of human macrodomains reveals novel activities and identifies PARG as most efficient ADPr-RNA hydrolase.Communications biology · 2025Article
- RACK1 MARylation regulates translation and stress granules in ovarian cancer cells.The Journal of cell biology · 2025Article
- Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.Neoplasia (New York, N.Y.) · 2025Article
- Adenosine diphosphate-ribosylation greatly affects proteins function: a focus on neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Insights into mechanisms of ubiquitin ADP-ribosylation reversal.Biochemical Society transactions · 2024Review
- PARP enzyme de novo synthesis of protein-free poly(ADP-ribose).Molecular cell · 2024Article
- Poly-ADP-ribosylation dynamics, signaling, and analysis.Environmental and molecular mutagenesis · 2024Review
- Dispensability of HPF1 for cellular removal of DNA single-strand breaks.Nucleic acids research · 2024Article
141 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 11 institutions in 4 countries.
Funding
Abstract
Adenosine diphosphate (ADP)-ribosylation is a post-translational protein modification implicated in the regulation of a range of cellular processes. A family of proteins that catalyse ADP-ribosylation reactions are the poly(ADP-ribose) (PAR) polymerases (PARPs). PARPs covalently attach an ADP-ribose nucleotide to target proteins and some PARP family members can subsequently add additional ADP-ribose units to generate a PAR chain. The hydrolysis of PAR chains is catalysed by PAR glycohydrolase (PARG). PARG is unable to cleave the mono(ADP-ribose) unit directly linked to the protein and although the enzymatic activity that catalyses this reaction has been detected in mammalian cell extracts, the protein(s) responsible remain unknown. Here, we report the homozygous mutation of the c6orf130 gene in patients with severe neurodegeneration, and identify C6orf130 as a PARP-interacting protein that removes mono(ADP-ribosyl)ation on glutamate amino acid residues in PARP-modified proteins. X-ray structures and biochemical analysis of C6orf130 suggest a mechanism of catalytic reversal involving a transient C6orf130 lysyl-(ADP-ribose) intermediate. Furthermore, depletion of C6orf130 protein in cells leads to proliferation and DNA repair defects. Collectively, our data suggest that C6orf130 enzymatic activity has a role in the turnover and recycling of protein ADP-ribosylation, and we have implicated the importance of this protein in supporting normal cellular function in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.