Structural biology of the writers, readers, and erasers in mono- and poly(ADP-ribose) mediated signaling

ADP-ribosylation of proteins regulates protein activities in various processes including transcription control, chromatin organization, organelle assembly, protein degradation, and DNA repair. Modulating the proteins involved in the metabolism of ADP-ribosylation can have therapeutic benefits in various disease states. Protein crystal structures can help understand the biological functions, facilitate detailed analysis of single residues, as well as provide a basis for development of small molecule effectors. Here we review recent advances in our understanding of the structural biology of the writers, readers, and erasers of ADP-ribosylation.

• Publication year

  2013

• Venue

  Molecular Aspects of Medicine

• Publication date

  2013-02-28

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.mam.2013.02.002PMID 23458732PMCID 3726583
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis.

  2013cited by this paper
• Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains.

  2013cited by this paper
• Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases

  2013cited by this paper
• Crystal Structure of Human ADP-ribose Transferase ARTD15/PARP16 Reveals a Novel Putative Regulatory Domain*

  2012influential reference
• The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks

  2012cited by this paper
• Dual roles of PARP-1 promote cancer growth and progression.

  2012cited by this paper
• Discovery of ligands for ADP-ribosyltransferases via docking-based virtual screening.

  2012cited by this paper
• Sirtuins: NAD(+)-dependent deacetylase mechanism and regulation.

  2012cited by this paper
• Structural basis of selective inhibition of human tankyrases.

  2012cited by this paper
• The 1.8 Å Cholix Toxin Crystal Structure in Complex with NAD+ and Evidence for a New Kinetic Model

  2012cited by this paper
• New readers and interpretations of poly(ADP-ribosyl)ation

  2012cited by this paper
• Structural insight into the interaction of ADP‐ribose with the PARP WWE domains

  2012cited by this paper
• Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase from Bacillus cereus*

  2012cited by this paper
• New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs

  2012cited by this paper
• Novel Binding Mode of a Potent and Selective Tankyrase Inhibitor

  2012cited by this paper
• Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment

  2012influential reference
• The diverse roles and clinical relevance of PARPs in DNA damage repair: current state of the art.

  2012cited by this paper
• Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a unique substrate-binding element

  2012cited by this paper
• Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors

  2012cited by this paper
• Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination.

  2012cited by this paper
• ADP-ribosylhydrolase 3 (ARH3), Not Poly(ADP-ribose) Glycohydrolase (PARG) Isoforms, Is Responsible for Degradation of Mitochondrial Matrix-associated Poly(ADP-ribose)*

  2012cited by this paper
• Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939.

  2012cited by this paper
• Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase

  2012cited by this paper
• Alternative Modes of Binding of Poly(ADP-ribose) Polymerase 1 to Free DNA and Nucleosomes*

  2012cited by this paper
• Structural Basis for DNA Damage–Dependent Poly(ADP-ribosyl)ation by Human PARP-1

  2012influential reference
• Crystal Structures of Poly(ADP-ribose) Polymerase-1 (PARP-1) Zinc Fingers Bound to DNA

  2011influential reference
• Orphan Macrodomain Protein (Human C6orf130) Is an O-Acyl-ADP-ribose Deacylase

  2011cited by this paper
• Poly(ADP-Ribose) (PAR) Binding to Apoptosis-Inducing Factor Is Critical for PAR Polymerase-1–Dependent Cell Death (Parthanatos)

  2011cited by this paper
• The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase

  2011cited by this paper
• Structural studies of the PARP-1 BRCT domain

  2011cited by this paper
• Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling

  2011cited by this paper
• The DNA-Binding Domain of Human PARP-1 Interacts with DNA Single-Strand Breaks as a Monomer through Its Second Zinc Finger

  2011cited by this paper
• Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease.

  2011cited by this paper
• RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling

  2011cited by this paper
• PARG is recruited to DNA damage sites through poly(ADP-ribose)- and PCNA-dependent mechanisms

  2011cited by this paper
• Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage

  2011cited by this paper
• Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism.

  2011influential reference
• Identification of Macrodomain Proteins as Novel O-Acetyl-ADP-ribose Deacetylases*

  2011cited by this paper
• Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death

  2011cited by this paper
• Structure and Biochemical Functions of SIRT6*

  2011cited by this paper
• Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer.

  2011cited by this paper
• Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose)

  2010cited by this paper
• Solution structure of a zinc‐finger domain that binds to poly‐ADP‐ribose

  2010cited by this paper
• Structure and identification of ADP-ribose recognition motifs of APLF and role in the DNA damage response

  2010cited by this paper
• Structural Basis of Poly(ADP-ribose) Recognition by the Multizinc Binding Domain of Checkpoint with Forkhead-associated and RING Domains (CHFR)*

  2010cited by this paper
• Toward a unified nomenclature for mammalian ADP-ribosyltransferases.

  2010cited by this paper
• Sirtuin chemical mechanisms.

  2010cited by this paper
• Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor.

  2010cited by this paper
• Structural and biophysical studies of human PARP-1 in complex with damaged DNA.

  2010cited by this paper
• Identification of a regulatory segment of poly(ADP-ribose) glycohydrolase.

  2010cited by this paper
• Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888.

  2010cited by this paper
• The Zn3 Domain of Human Poly(ADP-ribose) Polymerase-1 (PARP-1) Functions in Both DNA-dependent Poly(ADP-ribose) Synthesis Activity and Chromatin Compaction*

  2010cited by this paper
• The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets.

  2010cited by this paper
• Structural Basis for Substrate Recognition in the Enzymatic Component of ADP-ribosyltransferase Toxin CDTa from Clostridium difficile

  2009cited by this paper
• Cloning, expression, purification and crystallization as well as X-ray fluorescence and preliminary X-ray diffraction analyses of human ADP-ribosylhydrolase 1.

  2009influential reference
• Poly(ADP-ribose)–Dependent Regulation of DNA Repair by the Chromatin Remodeling Enzyme ALC1

  2009cited by this paper
• Learning how to read ADP-ribosylation.

  2009cited by this paper
• The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

  2009cited by this paper
• Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteome

  2009cited by this paper
• Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling

  2009cited by this paper
• Sensing NAD metabolites through macro domains.

  2009cited by this paper
• Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.

  2009influential reference
• Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites

  2009cited by this paper
• Mechanism of ADP-ribosylation removal revealed by the structure and ligand complexes of the dimanganese mono-ADP-ribosylhydrolase DraG

  2009cited by this paper
• A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation

  2009cited by this paper
• Crystal structure of dinitrogenase reductase-activating glycohydrolase (DraG) reveals conservation in the ADP-ribosylhydrolase fold and specific features in the ADP-ribose-binding pocket.

  2009cited by this paper
• Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.

  2009cited by this paper
• Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler

  2009influential reference
• The Crystal Structures of Chikungunya and Venezuelan Equine Encephalitis Virus nsP3 Macro Domains Define a Conserved Adenosine Binding Pocket

  2009influential reference
• Identification of the ADP-ribosylation sites in the PARP-1 automodification domain: analysis and implications.

  2009cited by this paper
• Domain C of human poly(ADP-ribose) polymerase-1 is important for enzyme activity and contains a novel zinc-ribbon motif.

  2008cited by this paper
• A Third Zinc-binding Domain of Human Poly(ADP-ribose) Polymerase-1 Coordinates DNA-dependent Enzyme Activation*

  2008influential reference
• Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation.

  2008cited by this paper
• Differential Activities of Cellular and Viral Macro Domain Proteins in Binding of ADP-Ribose Metabolites

  2008cited by this paper
• Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase.

  2008cited by this paper
• Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases.

  2008influential reference
• Zinc binding catalytic domain of human tankyrase 1.

  2008influential reference
• Needle in the haystack: structure-based toxin discovery.

  2008cited by this paper
• Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins

  2008cited by this paper
• Regulation of Insulin Secretion by SIRT4, a Mitochondrial ADP-ribosyltransferase*

  2007cited by this paper
• The New Zealand Asthma and Allergy Cohort Study (NZA2CS): Assembly, Demographics and Investigations

  2007cited by this paper
• SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells.

  2006cited by this paper
• The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases

  2006cited by this paper
• A steric antagonism of actin polymerization by a salmonella virulence protein.

  2006cited by this paper
• The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

  2006influential reference
• Structural and Functional Basis for ADP-Ribose and Poly(ADP-Ribose) Binding by Viral Macro Domains

  2006influential reference
• Identification and Characterization of a Mammalian 39-kDa Poly(ADP-ribose) Glycohydrolase*

  2006cited by this paper
• Structure and Notch receptor binding of the tandem WWE domain of Deltex.

  2005cited by this paper
• Identification of three critical acidic residues of poly(ADP-ribose) glycohydrolase involved in catalysis: determining the PARG catalytic domain.

  2005cited by this paper
• Regulation of Poly(ADP-ribose) Polymerase-1 by DNA Structure-specific Binding*

  2005cited by this paper
• Structural Basis for the Activation of Cholera Toxin by Human ARF6-GTP

  2005cited by this paper
• Structure and mechanism of ADP‐ribose‐1″‐monophosphatase (Appr‐1″‐pase), a ubiquitous cellular processing enzyme

  2005cited by this paper
• Splicing regulates NAD metabolite binding to histone macroH2A

  2005cited by this paper
• Exotoxin A–eEF2 complex structure indicates ADP ribosylation by ribosome mimicry

  2005cited by this paper
• Genetics and regulation of nitrogen fixation in free-living bacteria

  2005cited by this paper
• In silico characterization of the family of PARP-like poly(ADP-ribosyl)transferases (pARTs)

  2005cited by this paper
• Structural Basis of Severe Acute Respiratory Syndrome Coronavirus ADP-Ribose-1″-Phosphate Dephosphorylation by a Conserved Domain of nsP3

  2005cited by this paper
• Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition.

  2005cited by this paper
• Crystal structure of the C3bot–RalA complex reveals a novel type of action of a bacterial exoenzyme

  2005cited by this paper
• Tankyrase Polymerization Is Controlled by Its Sterile Alpha Motif and Poly(ADP-Ribose) Polymerase Domains

  2004cited by this paper

• Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage.

  2025cites this paper
• PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy

  2025cites this paper
• Development and Validation of a High‐Throughput Screening Assay for the Legionella ADP‐Ribosyl Transferase SdeA

  2025cites this paper
• PARP enzyme synthesis of protein-free poly(ADP-ribose): Implications for DNA damage signaling and repair.

  2025cites this paper
• Molecular insights into PARP1 activation: structural dynamics of DNA, NAD+, and zinc‑mediated allosteric regulation.

  2025cites this paper
• ADP-ribose hydrolases: biological functions and potential therapeutic targets

  2024cites this paper
• Poly‐ADP‐ribosylation dynamics, signaling, and analysis

  2024influential citation
• Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage

  2023cites this paper
• PARP-nucleic acid interactions: Allosteric signaling, PARP inhibitor types, DNA bridges, and viral RNA surveillance.

  2023cites this paper
• PARP1 is activated by membrane damage and is involved in membrane repair through poly(ADP‐ribosyl)ation

  2022cites this paper
• PARP-1 Is a Potential Marker of Retinal Photooxidation and a Key Signal Regulator in Retinal Light Injury

  2022cites this paper
• Proteome-wide microarray-based screening of PAR-binding proteins

  2022cites this paper
• A Long-Lasting PARP1-Activation Mediates Signal-Induced Gene Expression

  2022cites this paper
• Unconventional metabolites in chromatin regulation

  2022cites this paper
• Integrated, Integral, and Exploratory Biomarkers in the Development of Poly(ADP-Ribose) Polymerase Inhibitors

  2021cites this paper
• The BRCT domain of PARP1 binds intact DNA and mediates intrastrand transfer.

  2021cites this paper
• Structural and Functional Characterization of Legionella pneumophila Effector MavL

  2021cites this paper
• Reading ADP-ribosylation signaling using chemical biology and interaction proteomics.

  2021cites this paper
• PARPs in lipid metabolism and related diseases.

  2021cites this paper
• Poly(ADP-Ribosyl) Code Functions

  2021cites this paper
• Selective monitoring of the protein-free ADP-ribose released by ADP-ribosylation reversal enzymes

  2021cites this paper
• Repositioning PARP inhibitors for SARS‐CoV‐2 infection(COVID‐19); a new multi‐pronged therapy for acute respiratory distress syndrome?

  2020cites this paper
• Real-time monitoring of PARP1-dependent PARylation by ATR-FTIR spectroscopy

  2020cites this paper
• The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

  2020cites this paper
• HPF1 and nucleosomes mediate a dramatic switch in activity of PARP1 from polymerase to hydrolase

  2020cites this paper
• Transient decondensation of chromatin in liver nuclei of rats treated with tannic acid

  2020cites this paper
• PARPs and PAR as novel pharmacological targets for the treatment of stress granule-associated disorders.

  2019cites this paper
• ADP-ribosylation: from molecular mechanisms to human disease

  2019influential citation
• Regulating Immunity via ADP-Ribosylation: Therapeutic Implications and Beyond.

  2019cites this paper
• Emerging roles of ADP-ribosyl-acceptor hydrolases (ARHs) in tumorigenesis and cell death pathways.

  2019cites this paper
• Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis, characterization, antimicrobial activity and docking studies

  2019cites this paper
• Tannic Acid-induced Modulation of Poly(ADP-Ribose) Glycohydrolase and NAD+ Content in Rat Liver and Thymocyte Nuclei

  2019influential citation
• Hydrofluoric Acid-Based Derivatization Strategy To Profile PARP-1 ADP-Ribosylation by LC-MS/MS.

  2018cites this paper
• Comparative inhibitory profile and distribution of bacterial PARPs, using Clostridioides difficile CD160 PARP as a model

  2018cites this paper
• O-Linked N-Acetylglucosamine Transiently Elevates in HeLa Cells during Mitosis

  2018cites this paper
• Poly(ADP-ribose) polymerase 1 searches DNA via a ‘monkey bar’ mechanism

  2018cites this paper
• The comings and goings of PARP-1 in response to DNA damage.

  2018cites this paper
• PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow

  2018cites this paper
• Regulation of TGFβ signaling by long non-coding RNAs and ADP-ribosylation

  2018cites this paper
• Study of the Cellular Role of GRP78/BiP mono-ADP-ribosylation in UPR and Cancer

  2018cites this paper
• The ADP-Ribosyl-Transferases Diphtheria Toxin-Like (ARTDs) Family: An Overview

  2018influential citation
• Q-FADD: A mechanistic approach for modeling the accumulation of proteins at sites of DNA damage by free diffusion

  2018cites this paper
• PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

  2017cites this paper
• Enzymes in the Base Excision Repair Pathway as Targets for Small Molecule Mediated Therapeutics

  2017cites this paper
• PARP, transcription and chromatin modeling.

  2017cites this paper
• ADP-Ribosylation Reactions in Animals, Plants, and Bacteria

  2017cites this paper
• No Silver Bullet – Canonical Poly(ADP-Ribose) Polymerases (PARPs) Are No Universal Factors of Abiotic and Biotic Stress Resistance of Arabidopsis thaliana

  2017cites this paper
• A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale

  2016cites this paper
• Protein Arginine Methyltransferase 5 as a Driver of Lymphomagenesis

  2016cites this paper
• Fluorescent sensors of PARP-1 structural dynamics and allosteric regulation in response to DNA damage

  2016cites this paper
• Editorial (Thematic Issue: Overview on ADP Ribosylation and PARP Superfamily of Proteins).

  2016cites this paper
• Viral Macro Domains Reverse Protein ADP-Ribosylation

  2016cites this paper
• Inhibition of poly(adenosine diphosphate-ribose) polymerase using quinazolinone nucleus

  2016cites this paper
• Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review

  2015cites this paper
• Nuclear ADP-Ribosylation and Its Role in Chromatin Plasticity, Cell Differentiation, and Epigenetics.

  2015cites this paper
• Mechanistic Dissection of PARP 1 Trapping and the Impacton InVivo TolerabilityandEf fi cacyofPARP Inhibitors

  2015cites this paper
• Comparative structural analysis of the putative mono-ADP-ribosyltransferases of the ARTD/PARP family.

  2015cites this paper
• Functional characterization of chromatin-associated protein ADP-ribosylation

  2015cites this paper
• Past and current topics on ADP-ribosylation reactions.

  2015cites this paper
• Mechanistic Dissection of PARP1 Trapping and the Impact on In Vivo Tolerability and Efficacy of PARP Inhibitors

  2015cites this paper
• Clinical Trials of Poly(ADP-Ribose) Polymerase Inhibitors for Cancer Therapy: A Review.

  2015cites this paper
• Proteomics approaches to identify mono‐(ADP‐ribosyl)ated and poly(ADP‐ribosyl)ated proteins

  2015cites this paper
• Branching of poly(ADP-ribose): Synthesis of the Core Motif.

  2015cites this paper
• The rise and fall of poly(ADP-ribose): An enzymatic perspective.

  2015cites this paper
• Structures and Mechanisms of Enzymes Employed in the Synthesis and Degradation of PARP-Dependent Protein ADP-Ribosylation.

  2015cites this paper
• Endogenous ADP-Ribosylation

  2015cites this paper
• Post-Translational Modifications of Histones That Influence Nucleosome Dynamics

  2014cites this paper
• , Resonance Binding Assays Insights into PARP Inhibitors ' Selectivity Using Fluorescence Polarization and Surface Plasmon

  2014cites this paper
• NAD homeostasis in the bacterial response to DNA/RNA damage.

  2014cites this paper
• Insights into PARP Inhibitors’ Selectivity Using Fluorescence Polarization and Surface Plasmon Resonance Binding Assays

  2014cites this paper
• Chemical probes to study ADP-ribosylation: synthesis and biochemical evaluation of inhibitors of the human ADP-ribosyltransferase ARTD3/PARP3.

  2013cites this paper
• A fragment based 19 F-NMR screening Investigation of chemical probes for the poly ( ADP-ribose ) polymerases PARP 10 and PARP 14

  2013influential citation
• Poly(ADP-ribose): PARadigms and PARadoxes.

  2013cites this paper
• 50Years of poly(ADP-ribosyl)ation.

  2013cites this paper
• PARP inhibitors: polypharmacology versus selective inhibition

  2013cites this paper