Poly ADP-ribosylation of proteins. Processivity of a post-translational modification.
The nuclear enzyme poly(ADP-ribose) polymerase (EC 2.4.2.30) participates in DNA excision repair by post-translational selfmodification ("automodification") and the modification of other chromatin proteins ("heteromodification") with ADP-ribose polymers. We have studied the molecular mechanism of these reactions in a reconstituted in vitro system. After activation by DNA, poly(ADP-ribose) polymerase produces polymers with a distinct size pattern. These polymers are attached to a small subfraction of enzyme molecules. As the reaction progresses, more enzyme molecules are recruited for modification with an identical polymer size pattern. Likewise, the auto- and heteromodification reaction in nucleosomal core particles involves the consecutive addition of a highly conserved polymer size pattern to the acceptor proteins. Thus, a highly conserved polymer size pattern may constitute the molecular signal priming chromatin proteins for a role in DNA excision repair in vivo. The priming reaction is processive.
Naegeli
H
H
University of Zurich-Tierspital, Institute of Pharmacology and Biochemistry, Switzerland.
Loetscher
P
P
Althaus
F R
FR
D000818:Animals; D002417:Cattle; D004247:DNA; D004789:Enzyme Activation; D046911:Macromolecular Substances; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D046911:Macromolecular Substances; D009702:Nucleoside Diphosphate Sugars; D009707:Nucleosomes; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases