NDLI: Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D.

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Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D.

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Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Trask, D. K. Muller, M. T.
Description	Author Affiliation: Trask DK ( Department of Molecular Genetics, Ohio State University, Columbus 43210.);
Abstract	The activity of the endogenous DNA topoisomerase type I (EC 5.99.1.2) can be quantified in situ by determining how efficiently the enzyme is trapped in a covalent complex with DNA upon lysis of nuclei with detergents. In this way, we can measure relative levels of topoisomerase binding to DNA at native sites in chromatin. Since the majority of topoisomerase I is localized in the nucleolus at rRNA genes, we have evaluated how low levels of actinomycin D, which terminate transcription of rRNA genes, affect the activity of topoisomerase I. In vivo, as well as in vitro with purified topoisomerase I, we have found that drug treatment extends the half-life of the covalent topoisomerase-DNA complex. Actinomycin D stabilizes the nicked intermediate in the cleavage and resealing reaction but otherwise does not significantly alter the strand-passing ability of topoisomerase I. Sequence-specific cleavages by topoisomerase I were stimulated by actinomycin D at identical sequences recognized by the enzyme in the absence of drug. The localization of topoisomerase I in the nucleolus, coupled with the observation that transcription in this organelle is highly sensitive to actinomycin D and camptothecin treatment, leads us to propose that topoisomerase I contributes to actinomycin D inhibition of transcription.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	85
Language	English
Publisher	National Academy of Sciences
Publisher Date	1988-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Topoisomerases, Type I Metabolism DNA, Ribosomal Dactinomycin Pharmacology Transcription, Genetic Drug Effects Cell Line Cell Nucleolus Chemical Phenomena Chemistry DNA-Binding Proteins Temperature Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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