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Destabilization of Zn 2+ coordination in ADP‐ribose transferase (polymerizing) by 6‐nitroso‐1,2‐benzopyrone coincidental with inactivation of the polymerase but not the DNA binding function
Author(s) -
Buki Kalman G.,
Bauer Pal I.,
Mendeleyev Jerome,
Hakam Alaeddin,
Kun Ernest
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)81255-7
Subject(s) - klenow fragment , dna polymerase i , primer (cosmetics) , dna , microbiology and biotechnology , polymerase , biochemistry , transferase , dna polymerase , biology , dna replication , enzyme , chemistry , exonuclease , reverse transcriptase , polymerase chain reaction , organic chemistry , gene
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 Zn 2+ from one of the two zinc finger polypeptide complexes present in the intact enzyme, as determined by the loss of 50% of 65 Zn 2+ from the 65 Zn 2+ ‐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.