Characterization of DNA strand breakage in vitro by the antitumor protein neocarzinostatin

The antitumor protein antibiotic neocarzinostatin causes strand scission of DNA in vitro in the presence of a sulfhydryl compound. The breaks are single stranded in nature and bear 5'-phosphoryl termini. All four deoxymononucleotides are recoverable at the 5'-ends of the cleavage sites alt...

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Bibliographic Details
Published in:	Biochemistry (Easton) Vol. 16; no. 3; pp. 486 - 493
Main Authors:	Poon, Raymond, Beermann, Terry A, Goldberg, Irving H
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 08-02-1977
Subjects:	Antibiotics, Antineoplastic - pharmacology Base Sequence Centrifugation, Density Gradient Clostridium perfringens Coliphages DNA, Bacterial - metabolism DNA, Single-Stranded DNA, Viral - metabolism Escherichia coli - enzymology Kinetics Nucleic Acid Conformation Polynucleotide Ligases - metabolism Zinostatin - pharmacology
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Summary:	The antitumor protein antibiotic neocarzinostatin causes strand scission of DNA in vitro in the presence of a sulfhydryl compound. The breaks are single stranded in nature and bear 5'-phosphoryl termini. All four deoxymononucleotides are recoverable at the 5'-ends of the cleavage sites although a higher proportion of dGMP and TMP are consistently found. The lesions are not repairable with polynucleotide ligase from Escherichia coli. A quantitative assay was developed to determine the pH profile and time course of the reaction. Data from protection experiments with synthetic and natural DNAs indicate the requirement for thymidylic acid and deoxyadenylic acid in the DNA for cutting. In DNA-RNA hybrids, riboadenylic acid can substitute for deoxyadenylic acid, whereas ribouridylic acid cannot substitute for thymidylic acid. Release of thymine is detected, and the amount of release correlates well with the number of strand scissions.
Bibliography:	istex:028983BE7A59E62CC9373DF7BB107EDB65DBD0B5 ark:/67375/TPS-P18ZKGXT-F ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-2960 1520-4995
DOI:	10.1021/bi00622a023