GO-phase

Figure 20.1 (a) The cell cycle. For details see text, (b) k linear cell cycle. The process need not be cyclical stem cells may proliferate to produce daughter cells that differentiate and daughter cells that enter the Go phase where they remain for some time, indeed some may remain in Go until death (e.g. nerve cells). A stimulus, however, can cause a cell in go to enter the cycle (broken arrow). The numbers in parentheses indicate the time (in hours) that a human liver cell, in culture, takes to complete each phase. 

Normal cells have all the characteristics of fully differentiated cells specialized for a particular function. Their division is inhibited and they are usually in the Go phase of the cell cycle (see p. 394). Their external shape is variable and is determined by a strongly structured cytoskeleton. 

In most cell types, two further phases can be distinguished, Gi and G2 phase. Gi phase includes the period between M phase and S phase G2 phase covers the period between S phase and M phase. From Gi phase, the cell may transfer into a quiescent state known as Go phase. Appropriate signals (e.g., addition of growth factors) can induce the cell to return from Go into Gi phase and proceed with the cell cycle. 

When mitosis has been completed, the cell requires signals in the form of growth factors to direct towards a new roimd of division. The signals become effective in the first two-thirds of Gi phase. In this time window, the cell is programmed to begin a new cell cycle or to enter Go phase. After a particular point, the restriction point R, no further signals are needed to continue the cell cycle. The cell cycle apparatus is self-contained from this point onwards. S, G2 and M phase occur without external control. The cell cycle may still be halted after crossing the restriction point, however, if the cell detects, via internal control mechanisms or checkpoints, that defects have occurred in the correct course of the phases. 

Fig. 14.L Division activity and fate of a cell. Cells can move from a division-active state to a differentiated state or into the resting phase Go. The transition into Go phase is generaUy reversible, whereas differentiated cells often cannot return to the division-active state. The cell can be directed from all three stadia into programmed cell death, or apoptosis.

In the absence of external mitogenic signals or in the presence of a majority of antimi-togenic signals, cell division activity may be stopped. The cell enters the resting phase (Go phase). From Go phase, cell division may be resumed when mitogenic signals reappear. 

G2 Phase M Phase Mitosis (nuclear division) and GO Phase... 

After passing through mitosis and into Gl, a cell either continues through another division or ceases to divide, entering a quiescent phase (GO) that may last hours, days, or the lifetime of the cell. When a cell in GO begins to divide again, it reenters the division cycle through the Gl phase. Differentiated cells such as he-patocytes or adipocytes have acquired their specialized function and form they remain in the GO phase. 

Upon completion of the M phase, the cell transforms into two cells, which immediately enter a new cycle in Gl (the possibility of temporary arrest in a GO phase is considered elsewhere). 

Cells which have spent a long time in Gl lose some of the enzymes typically present in dividing cells — particularly those concerned with DNA synthesis. These cells have traditionally been said to be out of cycle or in GO. The implication of the GO-phase is that to leave GO-cells require a stimulus to urge them past a barrier and back into cycle. Pardee (1974) has suggested that whenever cells are exposed to suboptimal physiological conditions they enter a quiescent phase, and that there is a single restriction point in Gl which regulates their re-entry into a new round of the cell cycle. 

The requirements for epithelial cells are somewhat different (Reiss and Dibble, 1988). Mouse keratinocytes (MK-1 cells) enter a GO-phase within 24 h when confluent cultures are fed a serum-free, low Ca2+ (< 0.1 mM) medium supplemented with insulin, transferrin and sodium selenate (see 5.8). Addition of EGF (10 ng/ml) causes cells to enter S-phase after 10-12 h although the percentage of cells responding is not known. Insulin is not essential for this effect but apparently leads to a threefold increase on the rate of DNA synthesis measured 22-24 h after addition of EGF. TGF/ (100 pM) completely abolishes the effect of EGF. 

FBS FGF FITC GO-phase G1-phase G2-phase GMP, GDP, GTP foetal bovine serum fibroblast growth factor fluoroscein isothiocyanate the resting stage of the cell cycle the first gap in the cell cycle (between M and S) the second gap in the cell cycle (between S and M) guanosine monophosphate, diphosphate, triphosphate... 

Cellcycle is the sum of the processes occuring when a mother cell divides, forming two daughter cell. The cellcycle is divided into Gl, the period between the end of cell division and the start of DNA synthesis in the S phase. The S phase is followed by the G2 phase, which lasts until the M phase, mitosis, begins. Differentiated cells often enter a Go phase, a quiescent phase where they withdraw from the cell cycle and rest. 

At the cellular level, bursts of HA synthesis correlate with the onset of mitosis [34,35,63]. This disengages the cell from the ECM and tissue organization, and prepares the cell for the semi-autonomous situation required for cell division. At the completion of mitosis, or at the beginning of Go phase of the cell cycle, a burst of hyaluronidase expression may occur, removing the shell of pericellular HA, preparing the cell for re-association with the ECM... 

Figure 1 Overview of the different phases of the cell cycle. Quiescent cells are in GO phase and reenter the cell cycle at Gl during which cells prepare for DNA synthesis. After passing the restriction point in late Gl cells are committed to enter S phase, during which DNA replication occurs. Cells in G2 phase prepare for mitosis (M phase). Cell cycle progression is controlled by various positive and negative cell cycle regulatory proteins including cyclins (A, B, D, E) cyclin dependent kinases (cdk 1,2, 4, 6) cdk inhibitors (p15, p16, p18, p19, p21, p27, p57), retinoblastoma (Rb) and p53.

Fig. 5 The cell cycle. A proliferating cell goes through four phases an initial growth phase (Gl), a DNA synthesis phase (S), a second growth phase (G2), and, finally, a mitotic phase (M). During Gl the cell may also choose to differentiate into a new cell type or go into a quiescent state or GO phase. (View this art in color at www.dekker.com.)...

Fig. 5.2 GO phase diagram with respect to the chemical potentials of oxygen and hydrogen. Insets show the atomic structures of the corresponding GO phases (Adapted from Ref [46]. Copyright (2010) by the American Physical Society)...

Bleomycin degrades DNA to cause fragmentation of the strands. Bleomycin is most effective in the G2 phase and during mitosis of the cell cycle, but it is also effective against cells in the Go phase. 

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