Table Of Content37
Molecular Biology
Biochemistry and Biophysics
Edited by Marc Solioz
F. R. Althaus Ch. Richter
ADP-Ribosylation
of Proteins
Enzymology and Biological Significance
With 16 Figures
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Dr. FELIX R. ALTHAUS
UniversiHit Zurich
Institut fUr Pharmakologie und Biochemie
Winterthurer StraBe 260
CH-8057 Zurich
Dr. CHRISTOPH RICHTER
ETH-Zentrum
Laboratorium fUr Biochemie
UniversitiitsstraBe 16
CH-8092 Zurich
ISBN-13 :978-3-642-83079-2 e-ISBN-13 :978-3-642-83077-8
DOl: 10.1007/978-3-642-83077-8
Library of Congress Cataloging in Publication Data. Althaus, F. R. (Felix R.),
1949-. ADP-ribosylation of proteins. (Molecular biology, biochemistry, and
biophysics; 37) Includes bibliographies and index. 1. Adenosine diphosphate ribose.
2. Proteins-Metabolism. I. Richter, Ch. (Christoph), 1945-. II. Title. III. Series:
Molecular biology, biochemistry, and biophysics; v. 37) [DNLM: 1. Adenosine
Diphosphate Ribose-metabolism. 2. Nucleoside Diphosphate Sugars-meta
bolism. 3. Proteins-metabolism. WI Mo195T no. 37 / QU 58 A467a] QP625.
A.29A46 1987 599'.0133 87-12739
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Preface
In 1966, a paper entitled "On the formation of a novel adenylylic
compound by enzymatic extracts of liver nuclei" from Paul
Mandel's laboratory in Strasbourg, France, planted the seed for a
rapidly growing new field of biological research focusing on
ADP-ribosylation reactions. The development of this field over
the past 2 decades reflects very much a modern trend of biological
research. As more detailed knowledge accumulates, enigmatic
phenomena turn into concepts which create their own enigmata.
This process tends to favor the development of multiple, seemingly
disconnected, research lines until simplicity emerges from chaos
and unifying concepts substitute for controversy. It appears that
the field of ADP-ribosylation reactions has not yet attained this
latter stage. For example, with the identification of two different
classes of ADP-ribosylation reactions, i.e., mono-ADP-ribosyla
tion and poly-ADP-ribosylation reactions, the field split very early
into two separate branches of research. With the present volume,
we have divided the task of reviewing these two classes of ADP
ribosylation accordingly, although their coexistence in eukaryotes
may involve a closer functional linkage than hitherto recognized.
Some enzymes involved in ADP-ribose metabolism have not
yet acquired universally acceptable trivial names. The term
poly ( ADP-ribose)polymerase is most frequently used in the
literature, therefore, representing the term of choice in the present
volume, but the same enzyme has also been referred to as nuclear
ADP-ribosyltransferase, and poly(ADP-ribose)synthetase or
synthase. Very recently, the Enzyme Commission proposed the
name NAD+:poly(adenosine disphosphate D-ribose)ADP-D
ribosyltransferase [EC 2.4.2.30] for this enzyme.
The bibliography of this book was filed as of June 1986. We
have greatly benefited from the kind support of numerous
colleagues who provided us with preprints or reprints of their
recent work. We wish to thank them for their generous help. We
are especially indepted to our colleagues who generously gave of
their time for critical reading and comments on the manuscript.
Particular thanks go, in alphabetical order, to Drs. Rafael Alvarez
Gonzales, Peter A. Cerutti, Myron K. Jacobson, Eduard Jenny,
VIII Preface
Georg Mathis, Joel Moss, and Lloyd Vaughan. We also wish to
thank Mrs. Jeanne-Marie Burger for excellent secretarial work.
Spring 1987 FELIX R. ALTHAUS
CHRISTOPH RICHTER
Selected Review Articles Since 1980 Dealing with Various Aspects
of ADP-Ribosylation Reactions
Purnell MR, Stone PR, Whish WJD (1980) ADP-ribosylation of
nuclear proteins. Biochem Soc Trans 8:215-227
Mandel P, Okazaki H, Niedergang C (1982) Poly(adenosine
diphosphate ribose). Progr Nucl Acid Res Mol BioI 27:1-51
Hayaishi 0, Ueda K (eds) (1982) ADP-ribosylation reactions:
biology and medicine. Academic Press, London New York,
698 pp
Pekala PH, Moss J (1983) Poly ADP-ribosylation of proteins. Curr
Top Cellul Regul 22:1-49
Shall S (1984) ADP-ribose in DNA repair: a new component of
DNA excision repair. Adv Radiat BioI 11:1-69
Ueda K, Hayaishi 0 (1985) ADP-ribosylation. Annu Rev Biochem
54:73-100
Gaal JC, Pearson CK (1985) Eukaryotic nuclear ADP-ribosyla
tion reactions. Biochem J 230:1-18
Ueda K (1986) Nonredox reactions of pyridine nucleotides. In:
Dolphin D, Poulson R, Avranovic 0 (eds) Pyridine nucleotides.
Wiley, New York (in press)
Moss J, Vaughan M (1987) ADP-ribosylation of guanyl nucleotide
binding regulatory proteins by bacterial toxins. Adv Enzymol (in
press)
Contents
Part I Poly-ADP-Ribosylation Reactions
(F. R. ALTHAUS)
1 Poly(ADP-Ribose): Structure, Properties,
and Quantification
1.1 Structure and Physicochemical Properties . . . . . 3
1.2 Detection and Quantification of Poly(ADP-Ribose)
in Biological Material. 5
References . . . . . . . . . . . . . . . . . . 8
2 Poly(ADP-Ribose) Biosynthesis
2.1 Natural Occurrence of Poly-ADP-Ribosylation Activity
in Different Species, Tissues, and Cell Types . . . . 12
2.2 Subcellular Distribution of Poly-ADP-Ribosylation
Activity ............. . 15
2.3 Purified Poly(ADP-Ribose) Polymerase 16
2.3.1 Physicochemical Properties 16
2.3.2 Domain Structure . . . 19
2.3.3 Enzymological Properties 20
References . . . . . . 30
3 Poly(ADP-Ribose) Catabolism
3.1 Enzymes Involved in Poly(ADP-Ribose) Catabolism 38
3.2 Factors Affecting Poly(ADP-Ribose) Catabolism. 41
References . . . . . . . . . . . . . . . . . . 43
4 Nuclear Acceptor Proteins for Poly(ADP-Ribose) and
the Functional Consequences of Poly-ADP-Ribosylation
on the Acceptor Species
4.1 Acceptor Proteins Identified in Reconstituted in Vitro
Systems Involving Purified Poly(ADP-Ribose)
Polymerase . . . . . . . . . . . . . . . . . . . 50
XII Contents
4.2 Acceptor Proteins Identified in "Broken Cell" Systems
or Polynucleosomal Preparations . 51
4.3 Acceptor Proteins Which Have Been Identified
in Intact Cells 52
References 54
5 Poly-ADP-Ribosylation and Chromatin Organization
5.1 Introductory Comments. 59
5.2 Electron Microscopy Investigations of
Poly(ADP-Ribose)-Modified Chromatin. 60
5.3 Biochemical Analyses of Poly(ADP-Ribose)-Modified
Chromatin 61
5.4 Characterization of Sites Adjacent to
Poly-ADP-Ribosylation in Bulk Chromatin 63
References 63
6 Poly-ADP-Ribosylation in the Recovery of Mammalian
Cells from DNA Damage
6.1 Introduction. 66
6.2 DNA Damage, Activation of Poly(ADP-Ribose)
Polymerase, and NAD Depletion in Mammalian Cells. 67
6.3 Inhibitors of Poly(ADP-Ribose) Polymerase in the
Investigation of the Role of Poly-ADP-Ribosylation
Reactions in DNA-Excision Repair. 68
6.3.1 Specificity of Poly(ADP-Ribose) Polymerase Inhibitors 68
6.3.2 Inhibitor Protocols Used 70
6.3.3 Consequences of Inhibited Poly(ADP-Ribose)
Biosynthesis on Specific Reaction Steps in
DNA-Excision Repair of Mammalian Cells 72
6.4 Effects of ADP-Ribosylation Inhibitors on the Clonal
Survival of Carcinogen-Treated Cells 81
6.5 The Effects of ADP-Ribosylation Inhibitors
on Chromosome Stability . 82
6.6 Conclusions and Perspectives 83
References 84
7 Poly(ADP-Ribose), DNA Synthesis, and Cell Cycle
Progression
7.1 Proliferative Activity, Cell Cycle Progression, and
Chromatin-Associated ADP-Ribosylation Activity 93
7.2 Poly-ADP-Ribosylation and DNA Synthesis in Isolated
Nuclei 95
"
7.3 In Vitro Effects of Poly(ADP-Ribose) on Enzymes
Acting on DNA 96
References 97
Contents XIII
8 Poly(ADP-Ribose), Cellular Differentiation,
and Gene Expression
8.1 Introduction. . . . . . . . . . . . .. 101
8.2 Poly-ADP-Ribosylation in Differentiating Tissues
and Cells ............... . 101
8.3 Evidence Derived from Inhibitor Studies . . . . 104
8.4 Possible Mechanism(s) of Poly(ADP-Ribose)
Involvement in RNA Metabolism and Gene Expression 106
References . . . . . . . . . . . . . . . . 108
9 Poly(ADP-Ribose) in Inherited Human Diseases
and Experimental Disease Models
9.1 Glutamyl Ribose-5-Phosphate Storage Disease -
A Hereditary Defect in the Catabolism of
Poly(ADP-Ribosyl)ated Proteins . . . 114
9.2 Collagen Vascular Diseases . . . . . 115
9.2.1 Systemic Lupus Erythematosus (SLE) . 115
9.2.2 Other Collagen Vascular Diseases . . 116
9.3 Diseases Associated with Disorders of DNA Repair. 116
9.3.1 Xeroderma Pigmentosum (XP) . 116
9.3.2 Ataxia Teleangiectasia (AT) 117
9.3.3 Fanconi's Anemia (FA). . . . 117
9.4 Experimental Diabetes . . . . 118
9.5 Neoplastic Transformation in Vitro and in Vivo 118
9.5.1 In Vitro Transformation Systems . 119
9.5.2 Transformation in Vivo . 120
References 122
Part II Mono-ADP-Ribosylation Reactions
(CH. RICHTER)
Introduction
10 Signal Transduction
10.1 Introduction. . . . . . . . . . . . . . . . . 131
10.2 Guanine Nucleotide-Binding Regulatory Proteins
Involved in Signal Transduction 132
10.3 Adenylate Cyclase . . . . . . . . . . . . . . 132
10.4 Transducin . . . . . . . . . . . . . . . . . 135
10.5 Receptor-Stimulated Phosphodiesterase Stimulation
and Calcium Mobilization . 136
10.6 The ras Gene Product 137
References 138
