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

P. Bauer, Erzsebet Kenesi, Jerome Mendeleyev, Ernest Kun

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)321-324
Number of pages4
JournalInternational Journal of Molecular Medicine
Volume16
Issue number2
Publication statusPublished - Aug 2005

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Poly Adenosine Diphosphate Ribose
Adenosine Triphosphate
Fingers
Arginine
Poly(ADP-ribose) Polymerases
Glycoside Hydrolases
Energy Metabolism
Adenosine Diphosphate Ribose
Mutation
Cell Nucleus
Pharmaceutical Preparations
Mental Competency
Polymers
Amino Acids
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

The influence of ATP on poly(ADP-ribose) metabolism. / Bauer, P.; Kenesi, Erzsebet; Mendeleyev, Jerome; Kun, Ernest.

In: International Journal of Molecular Medicine, Vol. 16, No. 2, 08.2005, p. 321-324.

Research output: Contribution to journalArticle

Bauer, P, Kenesi, E, Mendeleyev, J & Kun, E 2005, 'The influence of ATP on poly(ADP-ribose) metabolism.', International Journal of Molecular Medicine, vol. 16, no. 2, pp. 321-324.
Bauer, P. ; Kenesi, Erzsebet ; Mendeleyev, Jerome ; Kun, Ernest. / The influence of ATP on poly(ADP-ribose) metabolism. In: International Journal of Molecular Medicine. 2005 ; Vol. 16, No. 2. pp. 321-324.
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