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Regulatory mechanisms of poly(ADP-ribose) polymerase

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ADP-Ribosylation Reactions: From Bacterial Pathogenesis to Cancer

Abstract

Here, we describe the latest developments on the mechanistic characterization of poly(ADP-ribose) polymerase (PARP) [EC 2.4.2.30], a DNA-dependent enzyme that catalyzes the synthesis of protein-bound ADP-ribose polymers in eucaryotic chromatin. A detailed kinetic analysis of the automodification reaction of PARP in the presence of nicked dsDNA indicates that protein-poly(ADP-ribosyl)ation probably occurs via a sequential mechanism since enzyme-bound ADP-ribose chains are not reaction intermediates. The multiple enzymatic activities catalyzed by PARP (initiation, elongation, branching and self-modification) are the subject of a very complex regulatory mechanism that may involve allosterism. For instance, while the NAD+ concentration determines the average ADP-ribose polymer size (polymerization reaction), the frequency of DNA strand breaks determines the total number of ADP-ribose chains synthesized (initiation reaction). A general discussion of some of the mechanisms that regulate these multiple catalytic activities of PARP is presented below.

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Authors and Affiliations

  1. The Department of Molecular Biology & Immunology, University of North Texas Health Science Center at Fort Worth, Texas, USA

    Rafael Alvarez-Gonzalez, Trent A. Watkins, Paramjit K. Gill, Jason L. Reed & Hilda Mendoza-Alvarez

  2. Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX, 76107-2690, USA

    Rafael Alvarez-Gonzalez

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  1. Rafael Alvarez-Gonzalez
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  2. Trent A. Watkins
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  3. Paramjit K. Gill
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  4. Jason L. Reed
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  5. Hilda Mendoza-Alvarez
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Editors and Affiliations

  1. Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 2500 Camp Bowie Boulevard, Fort Worth, TX, 76107, USA

    Rafael Alvarez-Gonzalez

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© 1999 Springer Science+Business Media New York

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Alvarez-Gonzalez, R., Watkins, T.A., Gill, P.K., Reed, J.L., Mendoza-Alvarez, H. (1999). Regulatory mechanisms of poly(ADP-ribose) polymerase. In: Alvarez-Gonzalez, R. (eds) ADP-Ribosylation Reactions: From Bacterial Pathogenesis to Cancer. Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8740-2_3

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  • DOI: https://doi.org/10.1007/978-1-4419-8740-2_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4678-4

  • Online ISBN: 978-1-4419-8740-2

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