Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Protein−Protein Interaction of the Human Poly(ADP-ribosyl)transferase Depends on the Functional State of the Enzyme

View Author Information
Institut für Biochemie, Freie Universität Berlin, Thielallee 63, D-14195 Berlin, Germany
Cite this: Biochemistry 1997, 36, 24, 7297–7304
Publication Date (Web):June 17, 1997
Copyright © 1997 American Chemical Society

    Article Views





    Other access options


    Poly(ADP-ribosyl)transferase (pADPRT) is a nuclear protein which catalyzes the polymerization of ADP-ribose using NAD+ as substrate, as well as the transfer of ADP-ribose polymers to itself and other protein acceptors. The catalytic activity of pADPRT strictly depends on the presence of DNA single-strand breaks. In this report, protein−protein interaction of pADPRT was found to depend on both the extent of automodification with poly(ADP-ribose) and the presence of DNA. Specific binding of radiolabeled pADPRT to transblotted proteins was first tested in blot overlay experiments. For radiolabeling, use was made of the ability of the enzyme to incorporate [32P]ADP-ribose from [32P]NAD+. Varying the concentration of NAD+, two different forms of automodified pADPRT were obtained:  oligo(ADP-ribosyl)ated pADPRT with less than 20 ADP-ribose units per chain, and poly(ADP-ribosyl)ated pADPRT with polymer lengths of up to 200 ADP-ribose residues. Interaction of these probes with transblotted HeLa nuclear extracts, purified histones, and distinct regions of recombinant pADPRT was investigated. While the oligo(ADP-ribosyl)ated enzyme associated preferentially with transblotted purified histones, or pADPRT present in HeLa nuclear extracts, poly(ADP-ribosyl)ated pADPRT bound to a variety of transblotted proteins in the nuclear extracts. In the presence of DNA, both the oligo- and the poly(ADP-ribosyl)ated enzymes bound to the transblotted recombinant zinc finger domain of pADPRT even at high salt concentrations. In the absence of DNA, the transblotted automodification domain of pADPRT appeared to be the region involved in self-association. In another set of experiments, unmodified or poly(ADP-ribosyl)ated pADPRT was immobilized on Sepharose. Affinity precipitation of recombinant pADPRT domains confirmed the specific interaction of pADPRT with its zinc finger region and the automodification domain, whereas no interaction was observed with the NAD+ binding domain. Affinity precipitation of HeLa nuclear extracts with poly(ADP-ribosyl)ated pADPRT−Sepharose led to the enrichment of a number of proteins, whereas nuclear proteins bound to the unmodified pADPRT−Sepharose in a smaller extent. The results suggest that protein−protein interaction of the human pADPRT is governed by its functional state.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.


    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

     This research was supported by grants from the Deutsche Forschungsgemeinschaft (SCHW 532/4-1) and the Studienstiftung des Deutschen Volkes.


     To whom correspondence should be addressed at the Institut für Biochemie, Freie Universität Berlin, Thielallee 63, D-14195 Berlin, Germany. Fax:  +49-30-838 6509. Phone:  +49-30-838 2910. E-mail:  [email protected].

     Abstract published in Advance ACS Abstracts, June 1, 1997.

    Cited By

    This article is cited by 33 publications.

    1. Ken Y. Lin, Dan Huang, W. Lee Kraus. Generating Protein-Linked and Protein-Free Mono-, Oligo-, and Poly(ADP-Ribose) In Vitro. 2018, 91-108.
    2. N. V. Maluchenko, O. I. Kulaeva, E. Yu. Kotova, A. A. Chupyrkina, D. V. Nikitin, M. P. Kirpichnikov, V. M. Studitsky. Molecular mechanisms of transcriptional regulation by Poly(ADP-ribose) polymerase 1. Molecular Biology 2015, 49 (1) , 86-98.
    3. Yizhou Dong, Susan L. Morris-Natschke, Kuo-Hsiung Lee. Biosynthesis, total syntheses, and antitumor activity of tanshinones and their analogs as potential therapeutic agents. Natural Product Reports 2011, 28 (3) , 529.
    4. Jing Wang, Xiujie Wang, Shu Jiang, Ping Lin, Jie Zhang, Yanrong Lu, Qi Wang, Zhujuan Xiong, Yaying Wu, Jingjing Ren, Hongliang Yang. Cytotoxicity of fig fruit latex against human cancer cells. Food and Chemical Toxicology 2008, 46 (3) , 1025-1033.
    5. Felicitas Berger, Corinna Lau, Mathias Ziegler. Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1. Proceedings of the National Academy of Sciences 2007, 104 (10) , 3765-3770.
    6. Jing Wang, Xiujie Wang, Shu Jiang, Shulan Yuan, Ping Lin, Jie Zhang, Yanrong Lu, Qi Wang, Zhujuan Xiong, Yaying Wu, Jingjing Ren, Hongliang Yang. Growth inhibition and induction of apoptosis and differentiation of tanshinone IIA in human glioma cells. Journal of Neuro-Oncology 2007, 82 (1) , 11-21.
    7. S. Wagner, M. Z. Hussain, S. Beckert, Q. P. Ghani, J. Weinreich, T. K. Hunt, H. D. Becker, A. Königsrainer. Lactate down‐regulates cellular poly(ADP‐ribose) formation in cultured human skin fibroblasts. European Journal of Clinical Investigation 2007, 37 (2) , 134-139.
    8. Claudia Keil, Tina Gröbe, Shiao Li Oei. MNNG-induced Cell Death Is Controlled by Interactions between PARP-1, Poly(ADP-ribose) Glycohydrolase, and XRCC1. Journal of Biological Chemistry 2006, 281 (45) , 34394-34405.
    9. M. V. Sukhanova, S. N. Khodyreva, O. I. Lavrik. Influence of poly(ADP-ribose) polymerase-1 and its apoptotic 24-kD fragment on repair of DNA duplexes in bovine testis nuclear extract. Biochemistry (Moscow) 2006, 71 (7) , 736-748.
    10. Xiujie Wang, Yuquan Wei, Shulan Yuan, Guanjian Liu, Yanrong Lu, Jie Zhang, Wendong Wang. Potential anticancer activity of tanshinone IIA against human breast cancer. International Journal of Cancer 2005, 116 (5) , 799-807.
    11. M. Malanga, M. Romano, A. Ferone, A. Petrella, G. Monti, R. Jones, E. Limatola, B. Farina. Misregulation of poly(ADP‐ribose) polymerase‐1 activity and cell type‐specific loss of poly(ADP‐ribose) synthesis in the cerebellum of aged rats. Journal of Neurochemistry 2005, 93 (4) , 1000-1009.
    12. Brian C. Beard, Jill J. Stevenson, Samuel H. Wilson, Michael J. Smerdon. Base excision repair in nucleosomes lacking histone tails. DNA Repair 2005, 4 (2) , 203-209.
    13. Min LI, Padmavathy NAIDU, Yihong YU, Nathan A. BERGER, Perry KANNAN. Dual regulation of AP-2α transcriptional activation by poly(ADP-ribose) polymerase-1. Biochemical Journal 2004, 382 (1) , 323-329.
    14. Jeppe Falsig, Søren Hofman Christiansen, Sascha Feuerhahn, Alexander Bürkle, Shiao Li Oei, Claudia Keil, Marcel Leist. Poly(ADP-ribose) glycohydrolase as a target for neuroprotective intervention: assessment of currently available pharmacological tools. European Journal of Pharmacology 2004, 497 (1) , 7-16.
    15. Claudia Keil, Eva Petermann, Shiao Li Oei. Tannins elevate the level of poly(ADP–ribose) in HeLa cell extracts. Archives of Biochemistry and Biophysics 2004, 425 (1) , 115-121.
    16. Brian C. Beard, Samuel H. Wilson, Michael J. Smerdon. Suppressed catalytic activity of base excision repair enzymes on rotationally positioned uracil in nucleosomes. Proceedings of the National Academy of Sciences 2003, 100 (13) , 7465-7470.
    17. Shiao Li Oei, Yang Shi. Transcription Factor Yin Yang 1 Stimulates Poly(ADP-Ribosyl)ation and DNA Repair. Biochemical and Biophysical Research Communications 2001, 284 (2) , 450-454.
    18. Sergei Storozhenko, Dirk Inzé, Marc Van Montagu, Sergei Kushnir. Arabidopsis coactivator ALY‐like proteins, DIP1 and DIP2, interact physically with the DNA‐binding domain of the Zn‐finger poly(ADP‐ribose) polymerase 1. Journal of Experimental Botany 2001, 52 (359) , 1375-1380.
    19. Mathias Ziegler, Shiao Li Oei. A cellular survival switch: poly(ADP‐ribosyl)ation stimulates DNA repair and silences transcription. BioEssays 2001, 23 (6) , 543-548.
    20. M. Malanga, B. Farina. Noncovalent Binding of Poly(ADP-Ribose) to Nuclear Matrix Proteins: Developmental Changes and Tissue Specificity. Biological Chemistry 2000, 381 (11) , 1047-1053.
    21. Shiao Li Oei, Mathias Ziegler. ATP for the DNA Ligation Step in Base Excision Repair Is Generated from Poly(ADP-ribose). Journal of Biological Chemistry 2000, 275 (30) , 23234-23239.
    22. Sydney Shall, Gilbert de Murcia. Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model?. Mutation Research/DNA Repair 2000, 460 (1) , 1-15.
    23. Mathias Ziegler. New functions of a long‐known molecule. European Journal of Biochemistry 2000, 267 (6) , 1550-1564.
    24. Philipp Mayer-Kuckuk, Oliver Ullrich, Mathias Ziegler, Tilman Grune, Manfred Schweiger. Functional Interaction of Poly(ADP-ribose) with the 20S Proteasome in Vitro. Biochemical and Biophysical Research Communications 1999, 259 (3) , 576-581.
    25. Jean-Christophe Amé, Véronique Rolli, Valérie Schreiber, Claude Niedergang, Françoise Apiou, Patrice Decker, Sylviane Muller, Thomas Höger, Josiane Ménissier-de Murcia, Gilbert de Murcia. PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase. Journal of Biological Chemistry 1999, 274 (25) , 17860-17868.
    26. Joachim Griesenbeck, Mathias Ziegler, Nikolai Tomilin, Manfred Schweiger, Shiao Li Oei. Stimulation of the catalytic activity of poly(ADP‐ribosyl) transferase by transcription factor Yin Yang 1. FEBS Letters 1999, 443 (1) , 20-24.
    27. Carlotta Trucco, Véronique Rolli, F. Javier Oliver, Eric Flatter, Murielle Masson, Françoise Dantzer, Claude Niedergang, Bernard Dutrillaux, Josiane Ménissier-de Murcia, Gilbert de Murcia. A dual approach in the study of poly (ADP-ribose) polymerase: In vitro random mutagenesis and generation of deficient mice. 1999, 53-60.
    28. Alison J. Butler, Charles P. Ordahl. Poly(ADP-Ribose) Polymerase Binds with Transcription Enhancer Factor 1 to MCAT1 Elements To Regulate Muscle-Specific Transcription. Molecular and Cellular Biology 1999, 19 (1) , 296-306.
    29. Shiao Li Oei, Joachim Griesenbeck, Manfred Schweiger, Mathias Ziegler. Regulation of RNA Polymerase II-dependent Transcription by Poly(ADP-ribosyl)ation of Transcription Factors. Journal of Biological Chemistry 1998, 273 (48) , 31644-31647.
    30. Murielle Masson, Claude Niedergang, Valérie Schreiber, Sylviane Muller, Josiane Menissier-de Murcia, Gilbert de Murcia. XRCC1 Is Specifically Associated with Poly(ADP-Ribose) Polymerase and Negatively Regulates Its Activity following DNA Damage. Molecular and Cellular Biology 1998, 18 (6) , 3563-3571.
    31. G. De Murcia, F. Dantzer, C. Trucco, V. Rolli, F. J. Oliver, C. Niedergang, J. Ménissier-De Murcia. Poly(ADP-Ribose) Polymerase Is Required for Maintenance of Genomic Integrity During Base Excision Repair. 1998, 83-102.
    32. Shiao Li Oei, Joachim Griesenbeck, Manfred Schweiger, Victor Babich, Andrey Kropotov, Nikolai Tomilin. Interaction of the Transcription Factor YY1 with Human Poly(ADP-Ribosyl) Transferase. Biochemical and Biophysical Research Communications 1997, 240 (1) , 108-111.
    33. Anna Reale, Giuseppe Zardo, Maria Malanga, Jordanka Zlatanova, Paola Caiafa. Inhibition of Poly(ADP-Ribosyl)ation Allows DNA Hypermethylation. , 142-155.