Molecular interactions between poly(ADP-ribose) polymerase (PARP I) and topoisomerase I (Topo I): Identification of topology of binding

Pal I. Bauer, Hui Je Chen, Erzsebet Kenesi, Istvan Kenessey, Kalman G. Buki, Eva Kirsten, Alaeddin Hakam, Jaulang I. Hwang, Ernest Kun

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)239-242
Number of pages4
JournalFEBS letters
Volume506
Issue number3
DOIs
Publication statusPublished - Oct 12 2001

Keywords

  • Binding site
  • Poly(ADP-ribose) polymerase I
  • Topoisomerase I binding
  • Topoisomerase I regulation by poly(ADP-ribose) polymerase I
  • Topology interaction

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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