Destabilization of Zn2+ coordination in ADP-ribose transferase (polymerizing) by 6-nitroso-1,2-benzopyrone coincidental with inactivation of the polymerase but not the DNA binding function

Kalman G. Buki, P. Bauer, Jerome Mendeleyev, Alaeddin Hakam, Ernest Kun

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

6-Nitroso- 1,2-benzopyrone, an oxidation product of 6-amino- 1,2-benzopyrone, binds to the DNA-recognizing domain of the ADP-ribose transferase protein and preferentially destabilizes Zn2+ from one of the two zinc finger polypeptide complexes present in the intact enzyme, as determined by the loss of 50% of 65Zn2+ from the 65Zn2+-isolated protein molecule, coincidental with the loss of 99% of enzymatic activity. The 50% zinc-deficient enzyme still binds to a DNA template. consisting of a 17-mer DNA primer annealed to M 13 positive strand, resulting in the blocking of DNA synthesis by the Klenow fragment of Pol I, Auto-poly-ADP-ribosylated ADP-ribose transferase, which is the probable physiological state of this protein in intact cells, does not bind to primer-template DNA and does not block DNA synthesis by the Klenow fragment. On the basis of this in vitro model it is proposed that molecules which inhibit or inactivate ADP-ribose transferase in intact cells can induce significant alteration in DNA structure and replication.

Original languageEnglish
Pages (from-to)181-185
Number of pages5
JournalFEBS Letters
Volume290
Issue number1-2
DOIs
Publication statusPublished - Sep 23 1991

Fingerprint

ADP Ribose Transferases
DNA-Directed DNA Polymerase
DNA Polymerase I
DNA Primers
DNA
Poly I
Proteins
Zinc
Zinc Fingers
Enzymes
DNA Replication
Adenosine Diphosphate
Molecules
Peptides
6-nitroso-1,2-benzopyrone
Oxidation

Keywords

  • 6-Nitroso-1.2-benzopyrone
  • ADP-ribose transferase
  • Zinc finger

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Destabilization of Zn2+ coordination in ADP-ribose transferase (polymerizing) by 6-nitroso-1,2-benzopyrone coincidental with inactivation of the polymerase but not the DNA binding function. / Buki, Kalman G.; Bauer, P.; Mendeleyev, Jerome; Hakam, Alaeddin; Kun, Ernest.

In: FEBS Letters, Vol. 290, No. 1-2, 23.09.1991, p. 181-185.

Research output: Contribution to journalArticle

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