title: Histone shuttle driven by the automodification cycle of poly(ADP-ribose)polymerase.
abstract: In mammalian cells, the incision step of DNA excision repair triggers a dramatic metabolic response in chromatin. The reaction starts with the binding of a zinc-finger protein, i.e. poly(ADP-ribose)polymerase to DNA nicks, activation of four resident catalytic activities leading to poly(ADP-ribose) synthesis, conversion of the polymerase into a protein modified with up to 28 variably sized ADP-ribose polymers, and rapid degradation of polymerase-bound polymers by poly(ADP-ribose)glycohydrolase. This automodification cycle catalyzes a transient and reversible dissociation of histones from DNA. Shuttling of histones on the DNA allows selected other proteins, such as DNA helicase A and topoisomerase I, to gain access to DNA. Histone shuttling in vitro mimics nucleosomal unfolding/refolding in vivo that accompanies the postincisional steps of DNA excision repair. Suppression of the automodification cycle in mammalian cells prevents nucleosomal unfolding and nucleotide excision repair.
authors.affiliation: University of Zürich-Tierspital, Institute of Pharmacology and Toxicology, Switzerland.
authors.forename: F R
authors.initials: FR
authors.lastname: Althaus
authors.forename: L
authors.initials: L
authors.lastname: Höfferer
authors.forename: H E
authors.initials: HE
authors.lastname: Kleczkowska
authors.forename: M
authors.initials: M
authors.lastname: Malanga
authors.forename: H
authors.initials: H
authors.lastname: Naegeli
authors.forename: P
authors.initials: P
authors.lastname: Panzeter
authors.forename: C
authors.initials: C
authors.lastname: Realini
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D006026:Glycoside Hydrolases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D006657:Histones; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase