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Inactivation of the Polymerase but not the DNA Binding Function of ADPRT by Destabilization of one of its Zn2+ Coordination Centers by 6-Nitroso-1,2-Benzopyrone

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ADP-Ribosylation Reactions

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Abstract

In the course of studies on the metabolism of inhibitors of poly (ADP- ribose) transferase (ADPRT), we observed that the inhibitor 6-amino-1,2-benzopyrone (6-ABP) (1) when metabolized by rat liver microsomal preparations is oxidized to the corresponding 6-nitroso derivative (6-NOBP) as the main metabolite (2). Since ADPRT is located in the nuclear matrix (3,4) and most of the cytochrome P450 resides in the endoplasmic reticulum which is contiguous with the nuclear membrane (5), generation of 6-NOBP near ADPRT is likely. This suggested that the exact cellular significance of this oxidation path be investigated with respect to ADPRT.

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Author information

Authors and Affiliations

  1. Laboratory for Environmental Toxicology and Chemistry and the Octamer Research Foundation, Romberg Tiburon Centers, San Francisco State University, Tiburon, CA, 94920, USA

    Kalman G. Buki, Pal I. Bauer, Jerome Mendeleyev, Alaeddin Hakam & Ernest Kun

  2. Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA, 94132, USA

    Kalman G. Buki, Pal I. Bauer, Jerome Mendeleyev, Alaeddin Hakam & Ernest Kun

Authors
  1. Kalman G. Buki
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  2. Pal I. Bauer
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  3. Jerome Mendeleyev
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  4. Alaeddin Hakam
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  5. Ernest Kun
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Editor information

Editors and Affiliations

  1. Centre de Recherches en Endocrinologie Moleculaire, Le Centre Hospitalier de l’Universite Laval, Quebec, G1V 4G2, Canada

    Guy G. Poirier

  2. Biochemistry Department Pavillon Vachon, Universite Laval, Quebec, G1K 7P4, Canada

    Pierre Moreau

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© 1992 Springer Science+Business Media New York

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Buki, K.G., Bauer, P.I., Mendeleyev, J., Hakam, A., Kun, E. (1992). Inactivation of the Polymerase but not the DNA Binding Function of ADPRT by Destabilization of one of its Zn2+ Coordination Centers by 6-Nitroso-1,2-Benzopyrone. In: Poirier, G.G., Moreau, P. (eds) ADP-Ribosylation Reactions. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8718-1_58

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  • DOI: https://doi.org/10.1007/978-1-4419-8718-1_58

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-6456-9

  • Online ISBN: 978-1-4419-8718-1

  • eBook Packages: Springer Book Archive

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