Regulatory mechanisms of poly(ADP-ribose) polymerase

Here, we describe the latest developments on the mechanistic characterization of poly(ADP-ribose) polymerase (PARP) [EC 2.4.2.30], a DNA-dependent enzyme that catalyzes the synthesis of protein-bound ADP-ribose polymers in eucaryotic chromatin. A detailed kinetic analysis of the automodification rea...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 1999-03, Vol.193 (1-2), p.19-22
Main Authors: Alvarez-Gonzalez, R, Watkins, T A, Gill, P K, Reed, J L, Mendoza-Alvarez, H
Format: Article
Language:English
Subjects:
Adenosine diphosphate
Adenosine Diphosphate Ribose - biosynthesis
Allosteric Regulation
Amino Acid Sequence
Catalysis
Deoxyribonucleic acid
DNA
Enzymatic activity
Enzymes
Poly(ADP-ribose) Polymerases - physiology
Polymers
Proteins
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Summary:Here, we describe the latest developments on the mechanistic characterization of poly(ADP-ribose) polymerase (PARP) [EC 2.4.2.30], a DNA-dependent enzyme that catalyzes the synthesis of protein-bound ADP-ribose polymers in eucaryotic chromatin. A detailed kinetic analysis of the automodification reaction of PARP in the presence of nicked dsDNA indicates that protein-poly(ADP-ribosyl)ation probably occurs via a sequential mechanism since enzyme-bound ADP-ribose chains are not reaction intermediates. The multiple enzymatic activities catalyzed by PARP (initiation, elongation, branching and self-modification) are the subject of a very complex regulatory mechanism that may involve allosterism. For instance, while the NAD+ concentration determines the average ADP-ribose polymer size (polymerization reaction), the frequency of DNA strand breaks determines the total number of ADP-ribose chains synthesized (initiation reaction). A general discussion of some of the mechanisms that regulate these multiple catalytic activities of PARP is presented below.
ISSN:0300-8177
1573-4919
DOI:10.1023/A:1006979220009