title: Histone shuttling by poly(ADP-ribosylation).
abstract: We have found that two nuclear enzymes, i.e. poly(ADP-ribose) polymerase (EC 2.4.2.30) and poly(ADP-ribose) glycohydrolase, may cooperate to function as a histone shuttle mechanism on DNA. The mechanism involves four distinct reaction intermediates that were analyzed in a reconstituted in vitro system. In the first step, the enzyme poly(ADP-ribose) polymerase is activated in the presence of histone-DNA complexes and converts itself into a protein carrying multiple ADP-ribose polymers. These polymers attract histones that dissociate from the DNA as a histone-polymer-polymerase complex. The DNA assumes the electrophoretic mobility of free DNA and becomes susceptible to nuclease digestion (second step). In the third step, poly(ADP-ribose) glycohydrolase degrades ADP-ribose polymers and thereby eliminates the binding sites for histones. In the fourth step, histones reassociate with DNA, and the histone-DNA complexes exhibit the electrophoretic mobilities and nuclease susceptibilities of the original complexes prior to dissociation. Our results are compatible with the view that the poly(ADP-ribosylation) system acts as a catalyst of nucleosomal unfolding of chromatin in DNA excision repair.
authors.affiliation: Institute of Pharmacology and Biochemistry, University of Zürich-Tierspital, Switzerland.
authors.forename: C A
authors.initials: CA
authors.lastname: Realini
authors.forename: F R
authors.initials: FR
authors.lastname: Althaus
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D006026:Glycoside Hydrolases; D006657:Histones / Q000378:metabolism*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases; D051381:Rats
chemical_list: D006657:Histones; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase