C. Stephen Downes

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Metaphase chromatids are believed to consist of loops of chromatin anchored to a central scaffold, of which a major component is the decatenatory enzyme DNA topoisomerase II. Silver impregnation selectively stains an axial element of metaphase and anaphase chromatids; but we find that in earlier stages of mitosis, silver staining reveals an initially(More)
The enzyme DNA topoisomerase II, which removes the catenations formed between the DNA molecules of sister chromatids during replication and is a structural component of chromosome cores, is needed for chromosome condensation in yeast and in Xenopus extracts. Inhibitors of topoisomerase II arrest mammalian cells before mitosis in the G2 phase of the cell(More)
We have used synchronized HeLa cells to investigate the role of the nuclear membrane in preventing rereplication in a single cell cycle. Nuclei were prepared with intact nuclear membranes using streptolysin-O or digitonin and assayed for replication in Xenopus egg extracts. Intact G1 nuclei replicate semiconservatively, but intact G2 nuclei do not replicate(More)
Gene expression profiling by microarray technology has been successfully applied to classification and diagnostic prediction of cancers. Various machine learning and data mining methods are currently used for classifying gene expression data. However, these methods have not been developed to address the specific requirements of gene microarray analysis.(More)
This article is a critical review of computational techniques used to model, analyse and simulate signalling networks. We propose a conceptual framework, and discuss the role of signalling networks in three major areas: signal transduction, cellular rhythms and cell-to-cell communication. In order to avoid an overly abstract and general discussion, we focus(More)
We have investigated the mechanism which prevents reinitiation of DNA replication within a single cell cycle by exploiting the observation that intact G2 HeLa nuclei do not replicate in Xenopus egg extract, unless their nuclear membranes are first permeabilized (Leno et al., 1992). We have asked if nuclear membrane permeabilization allows escape of a(More)
Inactivation of the TATA-binding protein-containing complex TFIIIB contributes to the mitotic repression of RNA polymerase III transcription, both in frogs and in humans (J. M. Gottesfeld, V. J. Wolf, T. Dang, D. J. Forbes, and P. Hartl, Science 263:81-84, 1994; R. J. White, T. M. Gottlieb, C. S. Downes, and S. P. Jackson, Mol. Cell. Biol. 15:1983-1992,(More)
MOTIVATION The protein tyrosine kinase Src is involved in a multitude of biochemical pathways and cellular functions. A complex network of interactions with other kinases and phosphatases obscures its precise mode of operation. RESULTS We have constructed a semi-quantitative computational dynamic systems model of the activation of Src at mitosis based on(More)
The cell division cycle is a fundamental process of cell biology and a detailed understanding of its function, regulation and other underlying mechanisms is critical to many applications in biotechnology and medicine. Since a comprehensive analysis of the molecular mechanisms involved is too complex to be performed intuitively, mathematical and(More)
Src family tyrosine kinases play a key role in many cellular signalling networks, but due to the high complexity of these networks their precise function remains elusive. Many factors involved in Src regulation, such as specific kinases and phosphatases, are still unknown. Mathematical models have been constructed to improve the understanding of the system(More)