PMID: 9057105Mar 1, 1997Paper

Daunomycin disrupts nuclear assembly and the coordinate initiation of DNA replication in Xenopus egg extracts

Journal of Cellular Biochemistry
F Leng, Gregory H Leno

Abstract

We have used Xenopus egg extracts to investigate the effects of the antitumor drug daunomycin on DNA replication in vitro. Xenopus sperm nuclei replicated nearly synchronously in our egg extracts, thereby allowing us to determine the effects of the drug on both replication initiation and elongation. Titration experiments demonstrated that daunomycin effectively inhibited replication in the extract, with 50% inhibition at a total drug concentration of 2.7 microM. However, a high concentration of daunomycin (50 microM) also inhibited nuclear envelope assembly, a prerequisite for the initiation of replication in this system. Therefore, to bypass the effects of daunomycin on nuclear envelope assembly, sperm nuclei were preassembled in extract prior to drug addition. Initiation of replication in preassembled nuclei was also inhibited by daunomycin, with 50% inhibition at a drug concentration of 3.6 microM. At low drug concentrations, where replication did occur, the synchrony of initiations within individual nuclei was lost. This drug-induced disruption of initiation events may provide important clues regarding the mechanism(s) by which these events are coordinated in eukaryotic cells. Daunomycin also inhibited replication elongatio...Continue Reading

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Citations

Feb 25, 2009·Nucleic Acids Research·Liliana Krasinska, Daniel Fisher
Dec 22, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Azra RabbaniJuan Ausió
Oct 18, 2000·International Journal of Biological Macromolecules·S J Zargar, A Rabbani

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