The influence of ATP on poly(ADP-ribose) metabolism

  • Authors:
    • Pal I. Bauer
    • Erzsebet Kenesi
    • Jerome Mendeleyev
    • Ernest Kun
  • View Affiliations

  • Published online on: August 1, 2005     https://doi.org/10.3892/ijmm.16.2.321
  • Pages: 321-324
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Abstract

ATP affects poly(ADP-ribose) metabolism at two distinct sites: it inhibits poly(ADP-ribose) polymerase-1 and activates the glycohydrolase directly. The inhibitory site of ATP on poly(ADP-ribose) polymerase-1 was identified by amino acid exchange mutation to be at the arginine 34 residue in the first Zn2+ finger. Mutation of 138 arginine residue of Zn2+ finger 2 had negligible influence on the inhibitory action of ATP, pinpointing arginine 34 of the first Zn2+ finger as the specific ATP site. The glycohydrolase protein was activated by ATP when the substrate was a long-chain ADP-ribose polymer, but not with a short-chain substrate. Isolated cell nuclei also responded to both inhibition of poly(ADP-ribose) polymerase by ATP and to poly(ADP-ribose) glycohydrolase activation by ATP, demonstrating that enzymological results can be extrapolated to cellular systems. The activation of poly(ADP-ribose) polymerase in nuclei by an alkylating drug was completely suppressed by ATP, demonstrating that the bioenergetic competence of cells can regulate the cytocidal action of DNA alkylating drugs. The potential significance of bioenergetic regulation of poly(ADP-ribose) metabolism is proposed.

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August 2005
Volume 16 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bauer PI, Kenesi E, Mendeleyev J and Kun E: The influence of ATP on poly(ADP-ribose) metabolism. Int J Mol Med 16: 321-324, 2005
APA
Bauer, P.I., Kenesi, E., Mendeleyev, J., & Kun, E. (2005). The influence of ATP on poly(ADP-ribose) metabolism. International Journal of Molecular Medicine, 16, 321-324. https://doi.org/10.3892/ijmm.16.2.321
MLA
Bauer, P. I., Kenesi, E., Mendeleyev, J., Kun, E."The influence of ATP on poly(ADP-ribose) metabolism". International Journal of Molecular Medicine 16.2 (2005): 321-324.
Chicago
Bauer, P. I., Kenesi, E., Mendeleyev, J., Kun, E."The influence of ATP on poly(ADP-ribose) metabolism". International Journal of Molecular Medicine 16, no. 2 (2005): 321-324. https://doi.org/10.3892/ijmm.16.2.321