G2 phase

Epipodophyllotoxins (etoposide, teniposide) are derived from mandrake root (Podophyllum peltatum). They inhibit topoisomerase H thus causing double strand breaks. Cells in S- and G2-phases are most sensitive. Unwanted effects include nausea and vomiting, myelosuppression, and hair loss. 

Rosenblatt, J., Yong, G., and Morgan, D. O. (1992). Human cyclin-dependent kinase 2 is activated during the S and G2 phases of the cell cycle and associates with cyclin A. Proc. Natl. Acad. Sci. USA 89 2824-2828. 

Eehner In the epidermis it is quite reproducible. After mitosis 13, when the syncytial division cycle is stopped, cellularization occurs followed by a pulse of string expression that allows cells to go through mitosis 14. Then they go immediately into S phase and wait in the next G2 phase until the next pulse of string comes up, driving mitosis 15. After mitosis 15, they go again immediately into S phase and wait in G2 until string comes up, triggering the final division. 

FIG. 1. Timing and morphology of mouse embryos during the first two cleavages. The cortical activity of the one-cell embryo begins during late G2 phase shortly before the entry into the mitotic M phase. Scheme represents shapes of embryos and morphology of their chromatin and microtubule cytoskeleton. 

FIG. 3. HistoneHl kinase activity and schematic representation of the morphology of one-cell mouse embryos (3A) and two-cell stage blastomeres (3B) bisected at the respective G2 phases. N ote that histone H1 kinase activity rises autonomously in anucleate halves of both embryos and blastomeres. However, the degree of the autonomous activation is lower than in theit nucleate counterparts. Activity detected in nucleate halves obtained during respective M phases was taken as 100%. Note that the nucleate halves obtained at theit respective G2 stages do not activate histone HI kinase to the levels observed in the halves obtained in the M phase, and that the mitotic disassembly of microtubules was observed only when the level of histone HI kinase was between 35% and 46% in anucleate halves. 

Vinblastine -vinca alkaloid inhibits tubulin polymerization G2 phase specific -bone marrow suppression -vesicant if extravasated -nausea and vomiting -constipation (often secondary to neuropathy induced ileus) -neuropathy (jaw pain, peripheral neuropathy, autonomic neuropathy) -SIADH -tumor pain... 

Cell cycle dynamics are closely connected to cell growth and to the mechanism of controlling cell proliferation. The cell cycle can be defined as an ordered set of biochemical events resulting in cell division. The sequence of these events is divided into four phases the Gi phase, followed by the S phase (DNA synthesis), G2 phase and the M phase. For determining percentage of cells at different phases of the cell cycle, cells must be stained for DNA content with propidium iodide (PI) [20, 21], Based on the amount of DNA content by PI, the fraction of cells in a specific phase can be determined [22] from whole population using dedicate software (e.g, Modfit or Flowjo ) or, more precise, by using 2D-dot plot BrdU incorporation [23],... 

Histone H3 (Til) phosphorylation occurs during mitosis by Dlk/ZIP kinase (Dlk Death-associated protein (DAP)-like kinase, ZIP Zipper interacting protein kinase) (Preuss et al, 2003) (Table 1). Histone H3 at Serine 28 is phosphorylated by Aurora B kinase at mitosis and this phosphorylation coincides with chromosome condensation (Goto et al., 1999, Goto et al, 2002) (Fig. 2), (Table 1). Histone H3 (S28) phosphorylation initiates at prophase, whereas histone H3 (SIO) phosphorylation initiates during the late G2 phase (Hendzel et al, 1997). 

In higher eukaryotes, at the onset of S phase cyclin A accumulates which stimulates DNA synthesis. The amount of cyclin A continues to be high after the S phase because of its role in chromosome condensation. Cyclin A is degraded when cells enter prometaphase. The level of another cyclin called cyclin B rises during G2 phase, which helps to complete the chromosome condensation and spindle assembly, which allow transition to metaphase. Cyclin B is degraded by APC during metaphase. ... 

Loss of purine or pyrimidine AP endonudease G2 phase of eukaryotic cell cycle ... 

Once the cycle has begun, the sequence of events is almost always completed in a time which is approximately constant for a given cell about 24 hours for a typical human cell. The largest variation in time occurs in the Gi phase. Very short cell cycles, 8 to 60 minutes, occur in early embryonic cells, during which cell division results in the formation of many smaller cells. In these cells, both the Gi and G2 phases are massively shortened, so that most of the time of cycling is spent in the S and M phases. 

The regulation of biochemical processes, described so far, in this book, is primarily the regulation of flux that is, the amount of biochemistry that is achieved in a certain period of time. In contrast, in the cycle, at least other than in the embryo, time is much less important. The important decision that a cell has to take is whether there are sufficient materials and fuels available in the preceding stage to allow the next step to proceed satisfactorily. If not, then the cycle must be arrested to prevent entry into the next phase. The cell, therefore, has to check if all the conditions are satisfactory, so that these positions of regulation are known as checkpoints. There are at least two one is present in the Gj phase, the other in the G2 phase (Figure 20.30). For example, DNA duplication can only proceed if ... 

Plitidepsin (Aplidin) (203) Cyclic depsipeptide Plitidepsin (Aplidin ) (203) Oncology Inhibitor to VEGF, VEGFRLandGl/ G2 phase cell cycle Phase II PharmaMar 934-936... 

In the cell cycle, dividing cells undergo one mitosis (M) after another, passing through Gi, S (DNA synthesis phase), and G2 phases. Some cells leave the cycle temporarily, entering a Go state from which they can be rescued by appropriate mitogenic stimuli. Other cells leave the cycle permanently, entering terminal differentiation. 

---