ADP-Ribosylation Reactions

ADP-Ribosylation Reactions: Biology and Medicine deals with the biochemical and physiological aspects of poly(ADP-ribose) and ADP-ribosylation of proteins. Topics covered range from pyridine nucleotide metabolism and ADP-ribosylation to the structure and properties of poly(ADP-ribose), along with acceptor proteins of poly(ADP-ribose). ADP-ribosyl protein linkages and poly(ADP-ribose) synthetase are also discussed. Comprised of 39 chapters, this book begins with a historical background on the discovery of poly(ADP-ribose) and the significance of poly- and mono(ADP-ribosyl)ation reactions in molecular biology. The next section explores the role of ADP-ribosylation in NAD metabolism, paying particular attention to poly(ADP-ribose) synthetase-DNA interaction and the link between chromatin structure and poly(ADP-ribosyl)ation. Subsequent chapters focus on subfractions and subcellular distribution of mono(ADP-ribosyl) proteins in eukaryotic cells; polyadenylylation and ADP-ribosylation of reovirus proteins; poly(ADP-ribose) synthesis in plants; and immunohistochemistry of poly(ADP-ribose). The final chapter analyzes the ADP-ribosylation activity of toxin A and exoenzyme S in Pseudomonas aeruginosa. This monograph is written for students, practitioners, and researchers in fields such as molecular biology, medical chemistry, and biochemistry.

ContributorsPrefacePart I Introduction 1 Poly- and Mono(ADP-Ribosyl)ation Reactions: Their Significance in Molecular Biology I. Prologue II. Discovery of Poly(ADP-Ribose) III. ADP-Ribosylation of Proteins IV. Prospects ReferencesPart II ADP-Ribosylation In NAD Metabolism 2 Pyridine Nucleotide Metabolism and ADP-Ribosylation I. Introduction II. Pyridine Nucleotide Biosynthesis III. Pyridine Nucleotide Cycles IV. Summary and Conclusions ReferencesPart III Poly(ADP-Ribosyl)ation A. Structure of Poly(ADP-ribosyl) Proteins (Chapters 3-6) Β. Poly(ADP-ribose) Biosynthesis and Degradation (Chapters 7-16) C. Natural Occurrence and Quantitation of Poly(ADP-Ribosyl) Proteins (Chapters 17-20) D. Functional Roles of Poly(ADP-Ribosyl)ation (Chapters 21-30) E. Poly(ADP-Ribose) in Medicine (Chapters 31-33) 3 Structure and Properties of Poly(ADP-Ribose) I. Structure of Poly(ADP-Ribose) II. Properties of Poly(ADP-Ribose) III. Conclusion References 4 DeoxyNAD and Poly(deoxyADP-Ribose) I. Introduction II. Synthesis and Characterization of 2'dNAD and 3'dNAD III. Template Activity of Nuclei Isolated from HeLa Cells with NAD, 2'dNAD, and 3'dNAD IV. Chain Length Determination V. ADP-Ribosylation of Isolated Rat Liver Nuclear Histone and Nonhistone Chromosomal Proteins by NAD and 2'dNAD VI. Chain Length Determination of ADP-Ribosylated Histone and Nonhistone Proteins in Isolated HeLa Nuclei Incubated with NAD or 2'dNAD VII. Characterization of the Ribose to Ribose 1" → 3' Osidic Bond Formed with 2'dNAD VIII. Discussion References 5 Acceptor Proteins of Poly(ADP-Ribose) I. Introduction II. Transfer of Mono- and Poly(ADP-Ribose) to Nuclear Proteins III. Isolation of Nuclear Poly(ADP-Ribose) Protein Conjugates Synthesized in Vitro IV. Identification of Individual Nuclear Proteins Serving as Acceptors for Mono- and Poly(ADP-Ribose) V. ADP-Ribosylation of Nuclear Proteins in Vivo VI. The Effect of DNA Damage on the ADP-Ribosylation of Nuclear Proteins in Vitro and in Vivo VII. ADP-Ribosylation of Nonnuclear Proteins VIII. Concluding Remarks References 6 ADP-Ribosyl Protein Linkages I. Introduction II. ADP-Ribosylation of Histones and Other Chromosomal Proteins III. ADP-Ribosylation of Histone H1 IV. ADP-Ribosylation of Nucleosomal Histones V. Chemical Stability of the ADP-Ribosyl-Protein Linkage VI. Chemical Nature of the ADP-Ribosyl-Protein Linkages References 7 Poly(ADP-Ribose) Synthetase I. Introduction II. Nomenclature and Standard Assay III. Distribution IV. Purification V. Physicochemical Properties VI. Enzymological Properties VII. Immunological Properties VIII. Regulation of Poly(ADP-Ribose) Synthetase References 8 Poly (ADP-Ribose) Synthetase—DNA Interaction I. Introduction II. DNA Structure Required for Enzyme Activation III. Study for Enzyme—DNA Interaction by Filter Binding Assay IV. Role of Mg2+ and Polyamines in Enzyme—DNA Interaction V. Summary References 9 Chromatin Structure and Poly(ADP-Ribosyl)ation I. Chromatin Structure II. Association of Poly(ADP-Ribose) Synthetase with Polynucleosomes III. Distribution of Acceptors of Poly(ADP-Ribose) in Oligo- and Polynucleosomes IV. NAD Concentration-Dependent Influence in the Modification of Nucleoprotein Complexes V. Modulation of Chromatin Structure by Poly(ADP-Ribosyl)ation—A Model References 10 Mitochondrial ADP-Ribosyltransferase System I. Introduction II. Materials and Methods III. Results IV. Discussion V. Summary References 11 Subfractions and Subcellular Distribution of Mono(ADP-Ribosyl) Proteins in Eukaryotic Cells I. Introduction II. Independent Synthesis of NH2OH-Sensitive and NH2OH-Resistant Mono(ADP-Ribose) Protein Conjugate During the Cell Cycle of Physarum Polycephalum III. Divergent Changes of Endogenous Mono(ADP-Ribosyl) Protein Subfractions in Eukaryotic Cells IV. Mono(ADP-Ribosyl) Proteins and Tissue Levels of NAD V. Subcellular Distribution of Mono(ADP-Ribosyl) Proteins VI. Mono(ADP-Ribosyl)ation of Proteins—A Multifunctional Process in Eukaryotic Cells References 12 Polyadenylylation and ADP-Ribosylation of Reovirus Proteins I. Introduction—Regulation of Reovirus Genome Expression II. Structural Features of Nucleotide-Modified Reovirus Polypeptides III. Synthesis of Modified Proteins in Virus-Infected Cells IV. Reovirion-Associated NAD-Dependent Nucleotide Transferase Activity V. Summary—The Role of Modified Proteins in Reovirus Replication Appendix References 13 Poly(ADP-Ribose) Synthesis in Plants I. Introduction II. A Survey of Posttranslational Protein Modifications in the Plant Nucleus III. Evidence and Properties of Poly(ADP-Ribose) Synthesis in Plant Nuclei IV. Conclusions References 14 ADP-Ribosylation in the Slime Mold Dictyostelium Discoideum I. Introduction II. Biological Characteristics of D. Discoideum III. ADP-Ribosylation in D. Discoideum IV. Conclusion References 15 Phosphodiesterases and Poly(ADP-Ribose) Glycohydrolase I. Introduction II. Phosphodiesterases (Pyrophosphatases) III. Poly(ADP-Ribose) Glycohydrolase References 16 ADP-Ribosyl Histone Hydrolase I. Introduction II. Preparation and Characterization of Substrates III. Enzyme Purification IV. Properties of ADP-Ribosyl Histone Hydrolase V. Heterogeneity of ADP-Ribosyl Histone Bonds VI. Properties of Split Product VII. Physiological Roles of ADP-Ribosyl Histone Hydrolase References 17 Isolation and Quantitation of Poly(ADP-Ribose) I. Introduction II. Methods Used III. Applications of These Methods IV. Conclusion V. Addendum References 18 Quantitation of Mono(ADP-Ribosyl) and Poly(ADP-Ribosyl) Proteins I. Introduction II. Determination of Protein-Bound Mono(ADP-Ribose) Residues III. Determination of Poly(ADP-Ribosyl) Proteins IV. Independence of Mono(ADP-Ribosyl)ation and Poly(ADP-Ribosyl)ation of Proteins as Deduced from the Determination of Endogenous ADP-Ribosyl Levels References 19 Electrophoretic Analysis of Poly(ADP-Ribosyl)ated HMG Proteins and Total Nuclear Proteins at Acidic pH and Low Temperature I. Introduction II. Methods III. Poly(ADP-Ribosyl)ated HMG Proteins and Histones of Pancreatic Chromatin IV. Discussion V. Summary References 20 Immunohistochemistry of Poly(ADP-Ribose) I. Introduction II. Procedures of Immunohistochemistry of Poly(ADP-Ribose) III. Specificity of Poly(ADP-Ribose) Immunofluorescent Staining IV. Observations with Immunohistochemistry of Poly(ADP-Ribose) V. Immunohistochemistry of Poly(ADP-Ribose) Synthetase VI. Perspectives References 21 DNA Replication and Poly(ADP-Ribosyl)ation I. Poly(ADP-Ribose) Synthetase Activity and Cell Proliferation II. Poly(ADP-Ribosyl)ation and DNA Synthesis III. DNA Repair, Recombination, and Chromosomal Condensation IV. Transformed and Tumor Cells V. Hormones and DNA Synthesis References 22 Variations in Poly(ADP-Ribose) and Poly(ADP-Ribose) Synthetase in Synchronously Dividing Cells I. Introduction II. Correlation between Poly(ADP-Ribose) Synthetase and Poly(ADP-Ribose) in Cells III. Inverse Correlation between Poly(ADP-Ribose) and Poly(ADP-Ribose) Glycohydrolase IV. Radioimmunoassay for Cellular Levels of Poly(ADP-Ribose) V. Effect of Poly(ADP-Ribose) Synthetase Inhibitors on Cellular Levels of Polymer and on Cell Growth VI. Effect of G2 Arresting Agents Which Are Not Direct Inhibitors of Poly(ADP-Ribose) Synthetase VII. Chromatin Conformational Changes and the Synthesis of Histone Η1—Poly(ADP-Ribose) Complex VIII. Summary References 23 Poly(ADP-Ribose) and the Differentiation of Embryonic Tissue I. Introduction II. The Embryonic Chick Limb Mesenchyme System III. Pool Sizes of Poly(ADP-Ribose) and Cartilage Differentiation IV. Poly(ADP-Ribose) Synthetase Activity During Mesenchymal Development V. Poly(ADP-Ribose) Synthetase Inhibitor Studies VI. Model and Summary References 24 Poly(ADP-Ribosyl)ation in Xenopus Laevis Embryos I. Introduction—Xenopus Laevis as a Biological System for Studying ADP-Ribosylation II. Methodology III. Results and Discussion IV. Concluding Remarks References 25 Poly(ADP-Ribose) and Differentiation of Mammalian Intestinal Epithelium I. Introduction—Intestinal Epithelium as a Regenerating and Differentiating Cell System II. Methodology III. Results and Discussion IV. Concluding Remarks References 26 Oxygen and Poly(ADP-Ribose) Synthesis in Myocardial and Skeletal Muscle I. Introduction II. Poly(ADP-Ribose) Metabolism in Cultured Heart Cells III. Poly(ADP-Ribose) Metabolism in Cultured Skeletal Muscle Cells References 27 Poly(ADP-Ribose) Synthetase Activity in Mitogen Stimulated Bovine Lymphocytes: Effects of Polyamines and Endogenous Nuclease Activity I. Introduction II. In Vitro Studies with Mitogen Stimulated Lymphocytes III. Nucleoid Sedimentation as a Probe of DNA Supercoiling IV. Discussion References 28 Glucocorticoid Effects on Poly(ADP-Ribose) Metabolism I. Introduction II. Changes in Poly(ADP-Ribose) Synthetase Activity of Chick Embryo Liver by Glycocorticoid Treatment III. Effect of Other Steroid Hormones on Poly(ADP-Ribose) Synthetase and Gene Activity IV. Concluding Remarks References 29 ADP-Ribose in DNA Repair I. Introduction II. DNA Damage and NAD Metabolism III. Effects of Inhibition of Poly(ADP-Ribose) Synthetase IV. Molecular Mechanism of Action of Poly(ADP-Ribose) Synthetase in DNA Excision Repair V. Implications for Chemotherapy and Carcinogenesis VI. Perspectives VII. Conclusions References 30 Poly(ADP-Ribose) as an Inhibitor of Chromatin Protease I. Introduction II. Chromatin-Bound Protease from Rat Peritoneal Macrophages III. Occurrence and Identification of Protease Inhibitor Activity IV. Control of the Protease by Poly(ADP-Ribose) in Vivo V. Concluding Remarks References 31 Systemic Lupus Erythematosus I. Introduction II. Experimentally Induced Antibodies to Poly(ADP-Ribose) III. Naturally Occurring Antibodies to Poly(ADP-Ribose) in Humans IV. Possible Functions of Double-Stranded RNA and Oligo(ADP-Ribosyl)ated Histones in Induction of Antibodies to Poly(ADP-Ribose) in SLE Patients V. Effects of Oligo(ADP-Ribosyl)ation of Histones on Histone Antigenicity VI. Concluding Remarks References 32 Poly(ADP-Ribose) in Xeroderma Pigmentosum and Related Disorders of DNA Repair I. Stimulation of Poly(ADP-Ribose) Synthesis by DNA Damage II. Defective Poly(ADP-Ribose) Synthesis in Xeroderma Pigmentosum Cells III. Poly(ADP-Ribose) Synthesis in Xeroderma Pigmentosum Cells Reconstituted with UV Endonuclease IV. Molecular Experiments to Define Sequence of Activation of Poly(ADP-Ribose) Synthetase by UV Irradiation V. Proposed Pathway for Poly(ADP-Ribose) Synthesis in Response to DNA Damage VI. Abnormalities of Poly(ADP-Ribose) Synthesis in Other Disorders of DNA Repair VII. Summary References 33 Leukemia and Cancer I. Poly(ADP-Ribose) in Neoplastic Tissues II. Poly(ADP-Ribose) and Differentiation of Neoplastic Cells III. Possible Relationship between Poly(ADP-Ribose) and Oncogenesis IV. Application of Poly(ADP-Ribose) Synthesis Modulators to Chemotherapy of Neoplasms ReferencesPart IV. Mono(ADP-Ribosyl)ation 34 Structure and Activity of Diphtheria Toxin I. Introduction II. Toxicity, Inhibition of Protein Synthesis, and ADP-Ribosylation Activity III. Structure—Activity Relationships IV. Concluding Remarks References 35 Cholera Toxin-Catalyzed ADP-Ribosylation of Membrane Proteins I. ADP-Ribosylation of Adenylate Cyclase II. Mechanism of the ADP-Ribosylation III. Other Activities of Cholera Toxin IV. Appendix: Conditions That Influence the Rate of ADP-Ribosylation References 36 Mechanism of Action of Escherichia Coli Heat-Labile Enterotoxin: Activation of Adenylate Cyclase by ADP-Ribosylation I. Introduction II. Evidence That the Enterotoxin Interacts Specifically with Ganglioside GM1 on the Cell Surface III. ADP-Ribosyltransferase Activity of E. Coli Heat-Labile Enterotoxin IV. Summary References 37 Purification and Properties of NAD:Arginine ADP-Ribosyltransferases from Animal Cells I. Characteristics of the Enzyme from Turkey Erythrocytes II. Identification of NAD:Arginine ADP-Ribosyltransferases in Other Tissues and Species III. Comparison of the Properties of the ADP-Ribosyltransferase from Turkey Erythrocytes with Those of Choleragen, E. Coli Heat-Labile Enterotoxin, and Viral Transferases IV. Summary References 38 T4 and N4 Phage-Encoded ADP-Ribosyltransferases I. Introduction II. ADP-Ribosyltransferases of Bacteriophage T4 III. ADP-Ribosyltransferase of Bacteriophage N4 IV. Conclusions References 39 Pseudomonas aeruginosa Toxin A and Exoenzyme S I. Introduction II. ADP-Ribosylation Activity of Toxin A and Exoenzyme S III. Structure-Function of Toxin A and Exoenzyme S IV. Production of Toxin A and Exoenzyme S V. Role of Toxin A and Exoenzyme S in P. aeruginosa Infections VI. Conclusions ReferencesIndex

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