The Mammalian Cell Cycle

The cell cycle is an ordered set of processes by which one cell grows and divides into two daughter cells: cell proliferation (Murray and Hunt, 1993). Two fundamentally different cell cycles exist in mammals: (i) the mitotic cell cycle, in which two diploid daughter cells are generated; and (ii) the meiotic cell cycle, in which four haploid daughter cells are produced (generation of sperm and egg). This chapter will focus exclusively on the mitotic cell cycle.

The absence of nutrients or growth factors causes cells to enter a specialized resting state called G0, during which they do not divide (Fig. 5.1) (Murray and Hunt, 1993). If supply with nutrients is sufficient, cells are recruited into the cell cycle by stimulation with compounds such as hormones, antigens and mitogens. The mitotic cell cycle can be thought of as occurring in two major sections:

Stimulation (e.g. mitogens or antigens)

Fig. 5.1. The cell cycle. Pie sections approximately parallel the percentage duration of the phases of the cell cycle. G0 = resting state; G, = gap 1 phase; S = DNA synthesis; G2 = gap 2 phase; M = mitosis.

interphase (which includes phases G1, S and G2) and mitosis. The cycle ends with the division of the cell.

  1. Interphase. The interphase is composed of three phases (Murray and Hunt, 1993): during the G1 phase, processes such as synthesis of membranes, mitochondria and most cellular proteins occur. During S phase, DNA is synthesized for duplication of chromosomes. Upon completion of S phase, cells enter G2 phase in which growth processes prepare the cell for mitosis ('M').
  2. Mitosis. Mitosis is subdivided into four phases (Murray and Hunt, 1993): during the first phase (prophase), the chromosomes condense (Fig. 5.2). In prometaphase, the membrane of the nucleus breaks down, and the chromosomes attach to microtubules, which are connected to centro-somes. In metaphase, the microtubule-bound chromosomes line up midway between the two centrosomes. Dissolution of the linkage between sister chromatids marks the beginning of anaphase; sister chromatids separate and move away from each other to opposite poles of the spindle. Finally, cytokinesis (the physical process of cell division) begins.

Cell proliferation is associated with a dramatic increase in the expression of certain genes. For example, mitogen-induced proliferation of human lymphocytes causes increased expression of genes such as c-myc, 4F1, JE-3, KC-1 (Kaczmarek et al., 1985), HsRAD51 (Flygare et al, 1996) and P120 (Wilson and Freeman, 1996). Likewise, cell proliferation is associated with increased rates of

Fig. 5.1. The cell cycle. Pie sections approximately parallel the percentage duration of the phases of the cell cycle. G0 = resting state; G, = gap 1 phase; S = DNA synthesis; G2 = gap 2 phase; M = mitosis.

┬ęCAB International 2003. Molecular Nutrition (eds J. Zempleni and H. Daniel)

Interphase Gap
Fig. 5.2. Mitosis.

metabolic flux through many metabolic pathways. For example, cell proliferation requires cell growth (e.g. synthesis of cell membranes) and doubling of DNA (Murray and Hunt, 1993). Nutrients are essential coenzymes (e.g. B vitamins), energy-providing substrates (e.g. glucose) and precursors (e.g. essential fatty acids) in many of the metabolic pathways that are essential for cell proliferation. In this chapter, we will provide evidence that cell proliferation is associated with increased expression of genes involved in nutrient uptake and metabolism. Furthermore, we will provide evidence that cell proliferation may generate an increased demand for nutrients. If not met, this increased demand may reduce cellular proliferation rates and impair cellular function.

0 0

Post a comment