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