title: Interactions of poly(ADP-ribose) with nuclear proteins.
abstract: The molecular mechanisms whereby poly(ADP-ribosyl)ation primes chromatin proteins for an active role in DNA excision repair are not understood. The prevalent view is that the covalent linkage of ADP-ribose polymers is essential for the modification of target protein function. By contrast, we have focused on the possibility that ADP-ribose polymers interact non-covalently with nuclear proteins and thereby modulate their function. The results show that ADP-ribose polymers engage in highly specific and strong non-covalent interactions with a small number of nuclear proteins, predominantly histones, and among these only with specific polypeptide domains. The binding affinities were largely determined by two factors, ie the polymer sizes and the presence of branches. This provides an explanation for the target specificity of the histone shuttle mechanism that was previously reported by our laboratory. Interestingly, the polymer molecules being most effective in protein targeting in vitro, are strictly regulated in mammalian cells during DNA repair in vivo.
authors.affiliation: University of Zürich-Tierspital, Institute of Pharmacology and Toxicology, Switzerland.
authors.forename: F R
authors.initials: FR
authors.lastname: Althaus
authors.forename: S
authors.initials: S
authors.lastname: Bachmann
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: P L
authors.initials: PL
authors.lastname: Panzeter
authors.forename: C
authors.initials: C
authors.lastname: Realini
authors.forename: B
authors.initials: B
authors.lastname: Zweifel
mesh_terms: D000818:Animals; D002460:Cell Line; D004260:DNA Repair; D006657:Histones / Q000737:chemistry; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry*; D011064:Poly Adenosine Diphosphate Ribose / Q000737:chemistry*; D012996:Solutions
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D012996:Solutions; D011064:Poly Adenosine Diphosphate Ribose