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    Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA 
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    Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA

    Volume
    72
    Pagination
    169 - 184
    DOI
    10.1016/S0301-4622%2898%2900132-X
    Journal
    Biophysical Chemistry
    Issue
    1-2
    ISSN
    0301-4622
    Metadata
    Show full item record
    Abstract
    Alternating phases of DNA synthesis and mitosis, during the first 12 cell divisions of frog embryos, are driven by autonomous cytoplasmic oscillations of M-phase promoting factor (MPF). Cell-free extracts of frog eggs provide a convenient preparation for studying the molecular machinery that generates MPF oscillations and the surveillance mechanism that normally prevents entry into mitosis until chromosomal DNA is fully replicated. Early experiments suggested that unreplicated DNA blocks MPF activity by inducing phosphorylation of a crucial tyrosine residue, but recent evidence implicates a stoichiometric inhibitor (an MPF binding protein) as the `braking' agent. Using a realistic mathematical model of the mitotic control system in frog egg extracts, we suggest that both tyrosine phosphorylation and a stoichiometric inhibitors are involved in the block of MPF by unreplicated DNA. Both pathways operate by raising the cyclin threshold for MPF activation. As a bonus, in the process of analyzing these experiments, we obtain more direct and reliable estimates of the rate constants in the model.
    Authors
    TYSON, CJ; Marlovits, G; Novak, B; Tyson, JJ
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/7589
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    • Economics and Finance [302]
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