Molecular interactions between poly(ADP-ribose) polymerase (PARP I) and topoisomerase I (Topo I): identification of topology of binding.
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.
Bauer
P I
PI
Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
Chen
H J
HJ
Kenesi
E
E
Kenessey
I
I
Buki
K G
KG
Kirsten
E
E
Hakam
A
A
Hwang
J I
JI
Kun
E
E
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
D004270:DNA, Circular; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase; D004264:DNA Topoisomerases, Type I