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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

Authors :
Ernest Kun
Pal I. Bauer
Kalman G. Buki
Jerome Mendeleyev
Alaeddin Hakam
Source :
FEBS Letters. (1-2):181-185
Publisher :
Published by Elsevier B.V.

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.

Details

Language :
English
ISSN :
00145793
Issue :
1-2
Database :
OpenAIRE
Journal :
FEBS Letters
Accession number :
edsair.doi.dedup.....dbf971c6ac77f6b6809e320ab5a96228
Full Text :
https://doi.org/10.1016/0014-5793(91)81255-7