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 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.
Alvarez-Gonzalez
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R
The Department of Molecular Biology & Immunology, University of North Texas Health Science Center at Fort Worth, 76107-2690, USA.
Watkins
T A
TA
Gill
P K
PK
Reed
J L
JL
Mendoza-Alvarez
H
H
D000246:Adenosine Diphosphate Ribose / Q000096:biosynthesis; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D002384:Catalysis; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*
D000246:Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases