Mitosis limiting factors

Control of translation at the level of initiation has also been reported in cultured mammalian cells during incubation at 42°C (McCormick and Penman, 1969) and during mitosis (Fan and Penman, 1969). The limiting factor for initiation at 42° appears to be an unidentified, labile RNA species, the synthesis of which is increased when translation is decreased. During mitosis the overall rate of protein synthesis is reduced... 

Phosphorylation of H3 is not limited to mitosis and also occurs in G1 phase of the cell cycle. Activation of the Ras-Raf-MEK-ERK signal transduction pathway and/or of the p38 stress kinase pathway when cells are treated with epidermal growth factor (EGF), 12-G-tetradecanoylphorbol-13-acetate (TPA), anesomycin, okadiac acid, and stresses such as UV irradiation induces the rapid phosphorylation of H3 at Ser-10 and/or Ser-28 [68-72] (Figs. 5 and 6). Inhibition of the MEK1,2 activity with PD98059 prevents the activation of ERK and TPA-induced H3... 

Whereas DNA s5mthesis takes place almost continuously in a rapidly growing bacterium, replication of DNA occupies a more limited part of the cell cycle of eukaryotes (Fig. 11-15). In a mammalian cell mitosis proper (Fig. 26-11) may require about one hour. It is followed by the "gap" period, Cy whose length is variable and depends upon the cell type, the nutritional state of the cell, and other factors. About 10 h is typical. During the S phase ( 9 h) active DNA replication takes place. This is followed by a second gap (G2) that occupies 4 h in the 24 h cell cycle shown in Fig. 11-... 

Wille, 1975). The division cycle occurs in these cells with a periodicity close to 12 h. Mixing experiments relying on the fusion of plasmodia taken at different times over the cycle showed phase advances or delays that would be typical of the behaviour expected if mitosis were driven by a continuous oscillator of a moderate relaxation nature (Kauffman, 1974 Kauffman Wille, 1975 Wille, Scheffey Kau an, 1977). Implicit in the limit cycle description is the assumption that one of the variables of the oscillator behaves as a mitogenic factor once this variable exceeds a certain threshold, mitosis would ensue. A specific prediction of the limit cycle model of mitosis is that finely tuned perturbations may transiently suppress oscillations. In this case, mitosis would eventually resume, with undefined phase, possibly after a delay corresponding to a few cycles in which the mitogenic factor oscillates below its threshold level. As the trajectory followed by the oscillator eventually approaches the asymptotic limit cycle, mitosis would occur when the threshold is again exceeded. 

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