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

FEBS Letters

Kenesi, Erzsebet²  Kun, Ernest¹  Bauer, Pal I.²  Hakam, Alaeddin¹  Kirsten, Eva¹  Hwang, Jaulang I.³  Buki, Kalman G.¹  Kenessey, Istvan²  Chen, Hui-Je³ 

[1] Department of Anatomy and Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, CA, USA;Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary;Department of Molecular Biology, Taipei University, Taipei, Taiwan

关键词: Poly(ADP-ribose) polymerase I;    Topoisomerase I binding;    Topoisomerase I regulation by poly(ADP-ribose) polymerase I;    Binding site;    Topology interaction;    PARP I;    poly(ADP-ribose) polymerase I;    Topo I;    topoisomerase I;    GST fusion polypeptides;    fusion products of Topo I polypeptides with glutathione S-transferase;   

DOI  :  10.1016/S0014-5793(01)02919-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown