title: Molecular interactions between poly(ADP-ribose) polymerase (PARP I) and topoisomerase I (Topo I): identification of topology of binding.
abstract: The molecular interactions of poly(ADP-ribose) polymerase I (PARP I) and topoisomerase I (Topo I) have been determined by the analysis of physical binding of the two proteins and some of their polypeptide components and by the effect of PARP I on the enzymatic catalysis of Topo I. Direct association of Topo I and PARP I as well as the binding of two Topo I polypeptides to PARP I are demonstrated. The effect of PARP I on the 'global' Topo I reaction (scission and religation), and the activation of Topo I by the 36 kDa polypeptide of PARP I and catalytic modifications by poly(ADP-ribosyl)ation are also shown. The covalent binding of Topo I to circular DNA is activated by PARP I similar to the degree of activation of the 'global' Topo I reaction, whereas the religation of DNA is unaffected by PARP I. The geometry of PARP I-Topo I interaction compared to automodified PARP I was reconstructed from direct binding assays between glutathione S-transferase fusion polypeptides of Topo I and PARP I demonstrating highly selective binding, which was correlated with amino acid sequences and with the 'C clamp' model derived from X-ray crystallography.
authors.affiliation: Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: P I
authors.initials: PI
authors.lastname: Bauer
authors.forename: H J
authors.initials: HJ
authors.lastname: Chen
authors.forename: E
authors.initials: E
authors.lastname: Kenesi
authors.forename: I
authors.initials: I
authors.lastname: Kenessey
authors.forename: K G
authors.initials: KG
authors.lastname: Buki
authors.forename: E
authors.initials: E
authors.lastname: Kirsten
authors.forename: A
authors.initials: A
authors.lastname: Hakam
authors.forename: J I
authors.initials: JI
authors.lastname: Hwang
authors.forename: E
authors.initials: E
authors.lastname: Kun
mesh_terms: D001665:Binding Sites; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004270:DNA, Circular / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D004270:DNA, Circular; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase; D004264:DNA Topoisomerases, Type I