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G 2 and M Phases of the Cell Cycle

G 2 and M Phases of the Cell Cycle. SIGMA-ALDRICH. G 2 and M Phases of the Cell Cycle

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G 2 and M Phases of the Cell Cycle

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  1. G2 and M Phases of the Cell Cycle SIGMA-ALDRICH

  2. G2 and M Phases of the Cell Cycle The transition from G2 phase to mitosis is triggered by the Cdc25-mediated activation (dephosphorylation) of the cyclin B/cdc2 complex (MPF). The activation of cyclin B/cdc2 that is necessary for G/M progression is currently the most well-characterized step in the cell cycle. CyclinB/cdc2 is activated by phosphorylation of Thr160 and the dephosphorylation of Thr14 -Tyr15. Thr160 is phosphorylated by cyclin activating kinase (CAK), following the activation of CAK by a cyclin activating kinase activating kinase (CAKAK). However, the complex is kept in an inactive state due to the phosphorylation of Thr15, which is catalyzed by the Wee1 kinase. Cyclin B/cdc2 activation is triggered when Cdc25, a phospatase, dephosphorylates Thr15. In turn, the activity of Cdc25 is regulated by both activating and inhibitory phosphorylations. Phosphorylation of Ser by Chk1 (a check point activated kinase that participates in the G2-arrest of cells with damaged DNA) leads to the inactivation of Cdc25, while phosphorylation by an M-phase activated kinase creates a positive feedback loop leading to the rapid activation of the cyclin B/cdc2 complex. MPF catalyzes the phosphorylation of lamins and histone 1, and is involved in the regulation of events preceding cell division, such as spindle formation, chromatin condensation, and fragmentation of the nuclear envelope and of organelles such as the Golgi and endoplasmic reticulum. The metaphase to anaphase transition is triggered by inactivation of MPF and the degradation of cyclin B. This induces the separation of chromatids and their movement to the poles of the mitotic spindle, after which the mitotic apparatus disappears, the nuclear membranes reform and the nucleoli reappear. During cytokinesis, the cytoplasm divides and the resulting daughter cells enter G1. References: Smits, V.A., and Medema, R.H., Checking out the G2/M transition. Biochim.Biophys.Acta., 1519, 1-12 (2001). Taylor, W.R., and Stark, G.R., Regulation of the G2/M transition by p53. Oncogene, 20, 1803-1815 (2001). Bulavin, D.V., et al., p38 and Chk1 kinases: different conductors for the G2/M checkpoint symphony. Curr. Opin. Genet. Dev., 12, 92-97 (2002).

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