Structure and Mechanism of a Canonical Poly(ADP-ribose) Glycohydrolase

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Jun 8

PMID 22673905

Citations 52

Authors

Mark S Dunstan

Eva Barkauskaite

Pierre Lafite

Claire E Knezevic

Amy Brassington

Marijan Ahel

Paul J Hergenrother

David Leys

Ivan Ahel

Affiliations

Soon will be listed here.

Abstract

Poly(ADP-ribosyl)ation is a reversible post-translational protein modification involved in the regulation of a number of cellular processes including DNA repair, chromatin structure, mitosis, transcription, checkpoint activation, apoptosis and asexual development. The reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) (PAR) glycohydrolase (PARG), which specifically targets the unique PAR (1''-2') ribose-ribose bonds. Here we report the structure and mechanism of the first canonical PARG from the protozoan Tetrahymena thermophila. In addition, we reveal the structure of T. thermophila PARG in a complex with a novel rhodanine-containing mammalian PARG inhibitor RBPI-3. Our data demonstrate that the protozoan PARG represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors.

Citing Articles

Discovery of reversing enzymes for RNA ADP-ribosylation reveals a possible defence module against toxic attack.

Lu Y, Schuller M, Bullen N, Mikolcevic P, Zonjic I, Raggiaschi R Nucleic Acids Res. 2025; 53(4).

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Insights into mechanisms of ubiquitin ADP-ribosylation reversal.

Zhang Z, Das C Biochem Soc Trans. 2024; 52(6):2525-2537.

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Investigating the Structure of the Components of the PolyADP-Ribosylation System in Fusarium Fungi and Evaluating the Expression Dynamics of Its Key Genes.

Stakheev A, Kutukov R, Taliansky M, Zavriev S Acta Naturae. 2024; 16(3):83-92.

PMID: 39555176 PMC: 11569842. DOI: 10.32607/actanaturae.27450.

Pathological and physiological roles of ADP-ribosylation: established functions and new insights.

Feijs-Zaja K, Ikenga N, Zaja R Biol Chem. 2024; .

PMID: 39066732 DOI: 10.1515/hsz-2024-0057.

PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair.

Andronikou C, Burdova K, Dibitetto D, Lieftink C, Malzer E, Kuiken H EMBO J. 2024; 43(6):1015-1042.

PMID: 38360994 PMC: 10943112. DOI: 10.1038/s44318-024-00043-2.

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