ADP-Ribose Transfer Reactions

Myron K. Jacobson Elaine L. Jacobson

Editors

ADP-Ribose Transfer Reactions

Mechanisms and Biological Significance

With 283 Illustrations

Springer-Verlag New York Berlin Heidelberg

London Paris Tokyo Hong Kong

Myron K. Jacobson

Department of Biochemistry Thxas College of Osteopathic Medicine furt Worth, Thxas 76107-2690 U.S.A.

Elaine L. Jacobson

Department of Medicine Texas College of Osteopathic Medicine furt Worth, Thxas 76107-2690 U.S.A.

Library of Congress Cataloging-in-Publication Data ADP-ribose transfer reactions : mechanisms and biological significance

/ Myron K. Jacobson, Elaine L. Jacobson, editors. p. cm.

ISBN-13:978-1-4615-8509-1 I. Adenosine diphosphate ribose-Metabolism. 2. NAD (Coenzyme)­

Metabolism. I. Jacobson, Myron K. II. Jacobson, Elaine L. QP625.A29A34 1989 574.19'25-dc20

© 1989 Springer-Verlag New York Inc. Softcover reprint of the hardcover 1st edition 1989

Copyright not claimed for employees of the United States Government.

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer-Verlag New York, Inc., 175 Fifth Avenue, New York, NY 10010, U.S.A.), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use of general descriptive names, trade names, trademarks, etc., in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Act, may accordingly be used freely by anyone.

Text prepared by the editors in camera-ready form.

9 8 7 6 5 432 I

ISBN-13:978-1-4615-8509-1 e-ISBN-13:978-1-4615-8507-7 DOl: 10.1007/978-1-4615-8507-7

This monograph is dedicated to Professor Helmuth Hilz of the University of Hamburg.

We would like to take this opportunity to acknowledge his many important contributions to our understanding of ADP-ribose transfer reactions and to express our appreciation for his advice, counsel and friendship.

Elaine L. Jacobson Myron K. Jacobson

Preface

The history of our understanding of the function of niacin and niacin­derived molecules in biological processes has evolved in three distinct phases. The first phase occurred between 1900 and 1940 and led to the discovery of nicotinic acid and nicotinamide a~ anti-pellagra factors. The second phase followed during the 1940's and 1950's and led to our understanding of the fundamental role of nicotinamide adenine dinucleotide, NAD, in hydride transfer reactions central to the energy metabolism of all living organisms. The topic of this monograph is the third and current phase: the role of NAD in ADP-ribose transfer reactions. While these reactions are still poorly understood, our current knowledge indicates that ADP-ribose transfer reactions are fundamentally involved in the regulation of many physiological processes. The contributions in this monograph are representative of current research in this rapidly expanding phase of our understanding of niacin metabolism.

The editors of this monograph are deeply indebted to the able and tireless work of Kay Hartman and Erica Castle, without whom this effort would not have been possible. We also thank Robin Chambers, Patrick Rankin and Ronaye Hubbard for their generous assistance.

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Contents

Part One: Enzymology of ADP.Ribosylation

Amino Acid-Specific ADP-Ribosylation: Purification and Properties of an Erythrocyte ADP-Ribosylarginine Hydrolase J. Moss, SOC. Tsai, R. Adamik, H-C. Chen, and S.J. Stanley .•................

ADP-RibosyItransferase and Endogenous Acceptor Proteins in Animal Muscle Tissues: ADP-Ribosylation of Ca2+-Dependent ATPase in Rabbit Skeletal Muscle Sarcoplasmic Reticulum and the Effect of Basic Peptides M Shimoyama, N. Hara, M. Tsuchiya, K. Mishima, and Y. Tanigawa ••........ 7

Endogenous ADP-Ribosylation of Proteins at Cysteine Residues B.L. Jacobson, M Mingmuang, N. Aboul-Ela, and M.K. Jacobson .•.......... 13

Reversible ADP-Ribosylation of Dinitrogenase Reductase from Rhodospirillum rubrum Regulates the Activity of the Enzyme In Vivo and In Vitro P.W. Ludden, S.A. Murrell, R.G. Lowery, W.P. Fitzmaurice, M.R. Pope, L.R. Saari, R.H. Kanemoto, and G.P. Roberts. . . . .. .. . . .. .................. . . . . .. 18

Phospho ADP-Ribosylation and Phospho Adenylylation of Proteins H. Hilz ............................................................ 26

ADP-Ribosyl Transferase of Mitochondria and of Ribonucleo­protein Particles Containing Silent Messenger RNA P. Mandel, A. Masmoudi, C. Chypre, and H. Thomassin .............•....... 32

In Vitro Evidence for POly(ADP-RibosyI)ation of DNA Polymerase a­Primase and Phosphorylation of Poly(ADP-Ribose) Synthetase by Protein Kinase C K. Yoshihara, Y. Tanaka, A. Itaya, T. Kamiya, T. Hironaka,T. Minaga, and S. Koide 39

POly(ADP-Ribose) Glycohydrolase and ADP-Ribosyl Group Turnover K. Hatakeyama, Y. Nemoto, K. Ueda, and O. Hayaishi . . . . . . . . . . . . . . . . . . . . . . . 47

In Vitro ADP-Ribosylation Utilizing 2'Deoxy-NAD+ as a Substrate R. Alvarez-Gonzalez, J. Moss, C.P. Niedergang, and F.R. Althaus

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53

Reconstitution of an In Vitro Poly(ADP.Ribose) Turnover System L. Menard, L. Thibault, A. Gaudreau, and G.G. Poirier. . . . . . . . . . . . . . . . . . . . . . . 57

Effect of Selected Octadeoxyribonucleotides and 6·Amino·l,2 Benzopyroneon Poly(ADP Ribose) Transferase Activity A. Hakam, I. Melick, K.G. Buki, and E. Kun ............................. 62

Two Tests of the Direction of Elongation ofPoly(ADP.ribose): Residues are Added at the Polymerase.Proximal Terminus M. Ikejima, G. Marsischky, andD.M. Gill ................................ 67

Biosynthesis and Degradation of Poly(ADP.Ribose) Synthetase I. Kameshita, Y. Mitsuuchi, M. Matsuda, and Y. Shizuta ..................... 71

Monoclonal Antibodies Against Poly(ADP.Ribose) Polymerase: Epitope Mapping, Inhibition of Activity and Interspecies Immunoreactivity D. Lamarre, G. de Murcia, B. Talbot, C. Laplante, Y. Leduc, and G.G. Poirier. . . . 76

Poly(ADP·Ribose) Polymerase: Determination of Content From TCA.Precipitated Cells, Existence of Species·Specific Isoforms and Changes During the Growth Cycle A. Ludwig and H. Hilz .................•..•.......................... 81

ADP.Ribosylation in Mitochondria: Enzymatic and Non Enzymatic Reactions A. Masmoudi and P. Mandel ...........•............•........•••...... 85

Localization of the Zinc.Binding Sites in the DNA.Binding Domain of the Bovine Poly(ADP.Ribose) Polymerase A. Mazen, D. Lamarre, G.G. Poirier, G. Gradwohl, and G. de Murcia . . . . . . . . . . . 89

Heterogeneity of Polyclonal Antisera to ADP·Ribose and Their Use as Probes for ADP.Ribosylation in Human Tumor Cells s.c. Prasad, P.I. Thraves, J. Boyle, and A. Dritschilo ........................ 94

ADP.Ribosylating Activity in Sulfolobus solfataricus P. Quesada, M. R. Farone-Mennella, M. De Rosa, A. Gambacorta, B. Nicolaus, and B. Farina. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . 101

Alteration ofPoly(ADP.Ribose) Metabolism By Ethanol: Kinetic Mechanism of Action J.L. Sims and R.C. Benjamin

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105

The Effect of Benzamides on the Activity of Nuclear ADP-Ribosyl Transferase and the Accumulation ofPoly(ADP-Ribose) In Vivo C.J. Skidmore, J. Jones, and B.N. Patel .........................•......... 109

Carba-Nicotinamide Adenine Dinucleotide: Synthesis and Enzymological Application of a Novel Inhibitor of ADP-Ribosyl Transfer J.T. Slama and A.M. Simmons ......................................... 113

Purification and Properties of Two Forms ofPoly(ADP-Ribose) Glycohydrolase S. Tanuma ..•........................................••............ 119

Poly(ADP-Ribosyl)ation in Free Cytoplasmic mRNA-Protein Complexes H. Thomassin and P. Mandel .......................................... 125

New Inhibitors of Poly(ADP-Ribose) Synthetase M. Banasik, R Komura, I. Saito, N.A.N. Abed, andK. Ueda ................ .. 130

Monoclonal Antibodies to Human Placental Poly(ADP-Ribose) Synthetase H. Ushiro and Y. Shizuta .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

Characterization of the Human Autoantibody Response to POly(ADP-Ribose) Polymerase H. Yamanaka, E. H. Willis, C. A. Penning, C. L. Peebles, E. M. Tan, and D.A. Carson........................................................ 139

In Vivo Automoditication of Poly(ADP-Ribose) Polymerase and DNA Repair J. Zhang, R. Kalamegham, and K. Ebisuzaki ..........•.•.......••.•..•... 145

Part Two: ADP-Ribosylation and Chromatin Function

ADP-Ribosylation and Chromatin Function F.R. Althaus, O. Mathis, R. Alvarez-Gonzalez, P. Loetscher, and M. Mattenberger 151

Modulation of Chromatin Structure by Poly (ADP-Ribosyl)ation A. Huletsky, O. de Murcia, S. Muller, D. Lamarre, M. Hengartner, and 0.0. Poirier 158

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Automodified Poly(ADP-Ribose) Synthetase Detected in Rat Liver Cells is Selectively Attached to a Nuclear Matrix-Like Structure M. Brauer, J. Witten, and P. Adamietz ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 165

Studies on the Nuclear Distribution of ADP-Ribose Polymers M.E. Cardenas-Corona, E.L. Jacobson, and M.K. Jacobson . . . . . . . . . . . . . . . . . . . 173

A Proposed Molecular Mechanism of Nucleosome Unfolding. Effect of Poly(ADP-Ribose) on DNA-Histone H4 Interaction G. Sauerrnann andJ. Wesierska-Gadek .................................. 179

On the Nature of the Interaction Between Poly(ADP-Ribose) Polymerase and DNA S.S. Sastry andE. Kun ............................................... 184

Inhibition of ADP-RibosyJ Transferase Activity Blocks the Stable Integration of Transfected DNA into the Mammalian Cell Genome F. Farzaneh, G.N. Panayotou, L.D. Bowler, T. Broom, and S. Shall ............ 189

Role of Poly(ADP-ribose) Polymerase in Ribosomal RNA Gene Transcription S.T. Jacob, J.F. Mealey, and R.N. Kurl ................................... 194

ADP-Ribosylation of HeLa Chromosomal and Nuclear Proteins: Response to DNA Damage Caused by Chemical Mutagens K.W. Adolph ....................................................... 200

Poly(ADP-Ribose) Polymerase: DNA Complexes Visualized as Looped Structures by Electron Microscopy G. Gradwohl, J. Dunand, A. Mazen, and G. de Murcia. . . . . . . . . . . . . . . . . . . . . . .. 206

Poly(ADP-Ribose) May Signal Changing Metabolic Conditions to the Chromatin of Mammalian Cells P. Loetscher, R. Alvarez-Gonzalez, and ER. Althaus ....................... 213

Uncoupling of DNA Excision Repair and Chromatin Rearrangements in Poly(ADP-Ribose)-Depleted Cells G. Mathis and F.R. Althaus ............................................ 218

Highly Sensitive Method for Immunohistochemical Detection ofPoly(ADP-Ribose) in Various Animal Species K. Nakagawa, P. Masahito, T. Ishikawa, H. Sugano, H. Kawamitsu, M. Miwa, and T. Sugimura .......... ... . . . .... .... .. . . . .... .. . ... ... . ...... . . . .... 222

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Part Three: Carcinogenesis and Differentiation

Poly(ADP-Ribosyl}ation of Nuclear Proteins By Oxidant Tumor Promoters P. Cerutti, G. Krupitza, and D. Miihlematter ................. . . . . . . . . . . . . .. 225

The Cytogenetic Effects of an Inhibition of Poly(ADP- Ribose} Polymerase W.F. Morgan, J.E. Cleaver, J.D. Shadley, J.K. Wieneke, and S. Wolff .......... 235

Effect of 3-Aminobenzamide on the Induction of 1- Glutamyltrans-peptidase Positive Foci in the Liver of Rats Treated with Various Chemical Carcinogens Y. Konishi, A. Denda, M. Tsutsumi, D. Nakae, and S. Takahashi .............. 242

A Role of Poly(ADP-Ribosyl}ation in Carcinogen-Inducible Transient DNA Amplification A. BUrkle, T. Meyer, H. Hilz, and H. zur Hausen ........................... 245

Arrest of Tumor Growth by DNA-Site Inhibitors of Adenosine Diphosphoribose Transferase E.Kun .•........ .... ....................... ... .................... 250

Inhibition of SV40 Replication In Vitro by Poly(ADP-Ribosyl)ated Diadenosine Tetraphosphate J. C. Baker, S. Smale, and B. N. Ames ............••...........•......... 254

Killing and Mutation of Density Inhibited V -79 Cells as Affected by Inhibition of Poly(ADP-Ribose) Synthesis N. Bhattacharyya, S. Das Gupta, and S.B. Bhattacharjee ..................... 261

Influence of Benzamide and Nalidixic Acid on the Killing and Mutation Induced in V-79 cells by N-Methyl-N'-Nitro-N­Nitrosoguanidine R. Ghosh (Datta) and S.B. Bhattacharjee ................................. 265

Loss ofPoly(ADP-Ribose) Transferase Activity in Liver of Rats Treated with 2-Acetylaminofluorene C.F. Cesarone, A.I. Seovassi, L. Searabelli, R. Izzo, M. Orunesu, and U. Bertazzoni 270

V-79 Cell Variants Deficient in Poly(ADP-Ribose) Polymerase S. Chatterjee, S.J. Petzold, S.J. Berger, and N.A. Berger ..................... 275

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Cytotoxicity ofTPA-StimulatedGranulocytesand Inhibitors of ADP-Ribosylation T. Meyer, A. Ludwig, H. Lengyel, G. Schafer, and H. Hilz ..........•••...... 279

3-Aminobenzamide Enhances X-Ray Induction of Chromosome Aberrations in Down Syndrome Lymphocytes R. A. MacLaren, W.W. Au, and M.S. Legator ............................. 283

3-Methoxybenzamide, A Possible Initiator for DMBA-Induced Carcinogenesis E.G. Miller, F. Rivera-Hidalgo, and W.H. Binnie ........................... 287

Synergistic Induction of Sister Chromatid Exchanges and Cell Division Delays in Ehrlich Ascites Tumor Cells Treated with Cytoxan and Caffeine In Vivo D. Mourelatos, J. Dozi-Vassiliades, A. Kotsis, and C. Gourtsas ................ 291

Inhibition of Poly(ADP-Ribosyl)ation and Sister Chromatid Exchange Induction J.L. Schwartz and P. Song . . . . . . . . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296

Dift'erential EtTect of Benzamide on Repair-Deficient and Proficient Strains of L5178Y Lymphoblasts Exposed to UVC or X-Radiations I. Szumiel, D. Wlodek, and KJ. Johanson ................................. 300

Nicotinamide Deficiency and Sister Chromatid Exchanges M. Tavassoli, K. Lindahl-Kiessling, and S. Shall ........................... 304

ADP-Ribosyl Transferase in the Dift'erentiation of Protozoa and Embryonic Mouse Thymus G.T. Williams, D.R. Taylor, E.J. Jenkinson, E. Grlffm, and M.E. Hill . . . . . . . . . . . 310

ADP-Ribosylation of Leukemia Cell Membrane Proteins Correlates with Granulocyte Colony-Stimulating Factor Dependent Dift'erentiation M-C. wu, M.R. Zaun, N. Aboul-Ela, and M.K. Jacobson. . . . . . . . . . . . . . . . . . . . .. 316

Poly(ADP-Ribose) Transferase in Lizard Oviduct G. Cian:ia, H. Suzuki, and M. Lancieri .............................. . . . . . 321

DNA Damage Does Not Induce Lethal Depletion of NAD During Chicken Spermatogenesis M. Corominas and C. Mezquita .........•........ " .•......•........... 326

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Divergence of POly(ADP-Ribose) Polymerase Activity, Poly(ADP­Ribose) Levels and the Effect of Polymerase Inhibitors in Differentiating 3T3-Ll Preadipocytes O. Janssen and H. Hilz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330

Differences in DNA Supercoiling and ADP-Ribosylation During Granulocytic and Monocytic Differentiation Z. Khan and G.B. Francis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334

Niacin Analogs that Induce Differentiation of Friend Erythro­leukemia Cells are Able to Cause DNA Hypomethylation J.R. Kuykendall and R. Cox . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339

In Vivo Poly(ADP-Ribose) Levels in Carcinogen Treated Human Promyelocytic Leukemia Cells B.N. Patel, M.B.J. Dover, and C.J. Skidmore ...........•.................. 345

Activation-Inactivation of Poly(ADP-Ribose) Transferase of Mammalian Cells Exposed to DNA Damaging Agents A.L Scovassi, M. Stefanini, R. Izzo, P. Lagomarsini, and U. Bertazzoni ., . • . . . . .. 348

Part Four: NAD Metabolism and Chemotherapy

Aspects of NAD Metabolism in Prokaryotes and Eukaryotes B.M. Olivera, K.T. Hughes, P. Cordray, and J.R. Roth .•..•.................. 353

An Approach to the Selective Targeting of NAD Consuming Reactions in Cultured Mammalian Cells M.K. Jacobson, P.W. Rankin, and E.L. Jacobson ..............•............. 361

Pyridine Nucleotide Metabolism as a Target for Cancer Chemotherapy N.A. Berger, S.J. Berger, and N.V. Hirschler .............................. 366

Pivotal Role of Poly(ADP-Ribose) Polymerase Activation in the Pathogenesis of Immunodeficiency and in the Therapy of Chronic Lymphocytic Leukemia C.J. Carrera, S. Seto, D.B. Wasson, L.D. Piro, E. Beutler, and D.A. Carson 372

Active Transport of Nicotinamide and the Adenine Moiety of NAD by Metabolically Controlled NAD Catabolism R.W. Pero, A. Olsson, T. Olofsson, and E. Kjellen .......................... 378

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The Effect of Extracellular Calcium on NAD Metabolism in Human Diploid Cells M.R. Duncan, P.W. Rankin, R.L. King, M.K. Jacobson, and R.T. Dell'Orco 386

Reduced Tumor Progression In Vivo by an Inhibitor of Poly (ADP-Ribose) Synthetase (3-Aminobenzamide) in Combination with X-Rays or Cytostatic Drug DTIC F. Darroudi, T.S.B. Zwanenburg, A.T. Natarajan, O. Driessen, and A. van Langevelde .................................................. 390

Cytotoxic Effects of 3-Aminobenzamide in CHO-KI Cells Treated with Purine Antimetabolites B.W. Durkacz, A.L. Harris, and K. Moses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 396

Hyperthermia and Poly (ADP-Ribose) Metabolism G. Jonsson, L. Menard., E.L. Jacobson, P.W. Rankin, G.G. Poirier, and M.K. Jacobson. . . . . . ... ... . .. ... . . . . ... . . . . .. . . . . .... .. . ... ... ... . . . 403

Comparison of Low Dose Nicotinamide Versus Benzamide as Radiosensitizers in a C3H Mammary Carcinoma E. Kjellen and R.W. Pero ............................................. 408

Viral Hepatitis in Mice and ADP-Ribose Metabolism H. Kroger, M. Klewer, K.N. Masihi, W. Lange, and B. Rohde-Schulz .......... 411

Part Five: ADP·Ribosylation and Signal Transduction

GTP-Binding Proteins, Substrates of Pertussis Toxin-Catalyzed ADP-Ribosylation, as Mediators of Receptor-Coupled Signal Transduction M. Ui ............................................................. 414

Clostridium botulinum Exoenzyme C3 ADP-Ribosylates and Functionally Modifies p21.bot in PCl2 Cells Without Mfecting Neurosecretion E.J. Rubin, P. Boquet, M.R. Popoff, and D.M. Gill .......................... 422

ADP-Ribosylation of Human c-Ha-ras Protein by Hen Liver ADP-Ribosyl Transferase H. Kawamitsu, M. Miwa, Y. Tanigawa, M. Shimoyama, S. Noguchi, S. Nishimura, and T. Sugimura ......................................... 430

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Mono(ADP-Ribosylation) in Rat Liver Mitochondria B. Frei and C. Richter ..•.............•.....•......................... 433

Botulinum Neurotoxins ADP-Ribosylate A Novel GTP­Binding Protein (Gb) S. Narumiya, Y. Ohashi, and M. Fujiwara. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 437

C3: A Novel Botulinum ADP-Ribosyltransferase Modifies a Putative 21 kDA G-Protein K. Aktories, M. Laux, and S. Rtlsener .................................... 445

Stimulation of Choleragen Enzymatic Activities by GTP and a Membrane Protein from Bovine Brain S-C. Tsai, M. Noda, R. Adamik, I. Moss, and M. Vaughan .................... 450

Activation of the NAD Glycohydrolase, NAD:Agmatine and NAD:Gsa ADP-RibosyItransferase and Auto-ADP-Ribosylation Activities of Choleragen by Guanyl Nucleotide and Soluble Proteins Purified from Bovine Brain M. Noda, S.-C. Tsai, R. Adamik, P.P. Chang, B.C. Kunz, I. Moss, and M. Vaughan 454

Part Six: Molecular Genetic Approaches to ADP­Ribosylation

Active Sites and Homology of Diphtheria Toxin and Pseudomonas aeruginosa Exotoxin A R.I. Collier . . • . • . . . • . . . • . . . . . . . . . • . . • . . . • • . . . . . . . . • . . • . . • . . . . . . . . . . . 458

The Cloning of the cDNA and Gene for Human Poly(ADP-Ribose) Polymerase: Status on the Biological Function(s) Using Recombinant Probes M. Smulson, H. Alkhatib, K. Bhatia, D. Chen, B. Chemey, V. Notario, C. Tahourdin, A. Dritschilo, P. Hensley, T. Breitman, G. Stein, Y. Pommier, O. McBride, M. Bustin, and C. Girl . . . . . . . • • . . . . • • . . • • . . . . .. .......•..... 463

Adenosine Diphosphate Ribosylation of Elongation Factor-2 as a Therapeutic Target: Genetic Construction and Selective Action of a Diphtheria Toxin-Related Interleukin-2 Fusion Protein D.P. Williams, P. Bacha, V. Kelley, T.B. Strom, andI.R. Murphy.............. 478

Molecular Structure of Poly(ADP-Ribose) Synthetase Y. Shizuta, T. Kurosaki, H. Ushiro, S. Suzuki, Y. Mitsuuchi, M. Matsuda , K. Toda, Y. Yokoyama, Y. Yamamoto, andK. Ito.......................... 487

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The Biological Function(s) of the Poly(ADP-Ribose) Polymerase as Observed by Transient Expression of the cDNA and Transcriptional Regulation of the Gene K. Bhatia, Y. Pommier, A. Fornace, T. Breitman, B. Cherney, C. Girl, and M. Smulson .•...................................................... 494

Rapid Isolation of ADP-Ribosyl Transferase by Specific Precipitation and Partial Sequencing of its DNA-Binding Domain K.G. Buki, E. Kirsten, and E. Kun . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 502

Sequence Analysis of the DNA Associated with Poly(ADP-Ribose) Polymerase Molecules M-E. Ittel, I-M. Ieltsch, and C.P. Niedergang .............................. 505

Molecular Cloning of cDNA for Human Placental Poly(ADP­Ribose) Polymerase and Decreased Expression of its Gene during Retinoic Acid-Induced Granulocytic Differentiation of HL-60 Cells H. Suzuki, K. Uchida, H. Shima, T. Sato, T. Okamoto, T. Kimura, T. Sugimura, andM.Miwa ..... .......... ...... ....... .......... ... .......... .... 511

Isolation of a cDNA Clone Encoding Bovine Poly(ADP-Ribose) Synthetase by Immunological Screening of a cDNA Expression Library and its Application as a Probe T. Taniguchi, K. Yamauchi, T. Yamamoto, K. Toyoshima, N. Harada, H. Tanaka, S. Takahashi, H. Yamamoto, and S. Fujimoto. . . . . . . . . . . ... . . . . .. . ...... . .. 515

Radiation Sensitivity of Human Cells and the Poly(ADP-Ribose) Polymerase Gene P.I. Thraves, K. Bhatia, M.E. Smulson, and A. Dritschilo . . . . . . . . . . . . . . . . . . . . . 520

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