Cell Division

Cell division, or mitosis, which was first described in 1875, is the process during which a parent cell divides and each daughter cell receives a chromosomal karyotype identical to the parent cell. Cell division gives the body a means of replacing cells that have a limited life span, such as skin and blood cells; increasing tissue mass during periods of growth; and providing for tissue repair and wound heal­ing. Despite the early cytologic description of the four stages of mitosis, it was not until the early 1950s that the importance of the cell cycle was realized.

 

FIGURE 4-12 Cell cycle. G₀, nondividing cell; G₁, cell growth; S, DNA replication; G₂, protein synthesis; M, mitosis, which lasts for 1 to 3 hours and is followed by cytokinesis or cell division. (teleophase [T], anaphase [A], mitosis [M], prophase [P])

Mitosis, which is a dynamic and continuous process, usually lasts from 1 to \V₂ hours. It is divided into four stages: prophase, metaphase, anaphase, and telophase (Fig. 4-13). The phase during which the cell is not under­going division is called interphase. During prophase, the chromosomes become visible because of increased coil­ing of the DNA, the two centrioles replicate, and a pair moves to each side of the cell. Simultaneously, the micro-tubules of the mitotic spindle appear between the two pairs of centrioles. Later in prophase, the nuclear enve­lope and nucleolus disappear. Metaphase involves the or­ganization of the chromosome pairs in the midline of the cell and the formation of a mitotic spindle composed of the microtubules. Anaphase is the period during which separation of the chromosome pairs occurs, with the micro­tubules pulling one member of each pair of 46 chromo­somes toward the opposite cell pole. Cell division, or cytokinesis, is completed after telophase, the stage during which the mitotic spindle vanishes and a new nuclear

 

THE CELL CYCLE AND CELL DIVISION

>- The cell cycle, which represents the life of a cell, is divided into two main phases: the synthesis or S phase, during which DNA is replicated and the M phase, during which mitosis occurs.

t*- Extra gaps are inserted to allow for growth and protein-G1 to prepare for the S phase and G₂ to prepare for the M phase.

>- A third gap, G₀, provides a time for cells to leave the cell cycle.

 

FIGURE 4-1 3 Cell mitosis. A and H represent the non-dividing cell; B, C, and D represent prophase; E and F represent anaphase; and G represents telophase.

membrane develops and encloses each complete set of chromosomes.

Cell division is controlled by changes in the intracel-lular concentrations and activity of three major groups of intracellular proteins: (1) cyclins, (2) cyclin-dependent ki-nases, and (3) the anaphase-promoting complex. The cen­tral components of the cell cycle control system are the cyclin-dependent kinases, whose activity depends on asso­ciation with the regulatory units called cyclins. Oscillations in the activity of the various cyclin-dependent kinases lead to initiation of the different phases of the cell cycle. For ex­ample, activation of the S-phase cyclin-dependent kinases initiates the S phase of the cell cycle, whereas activation of the M-phase cyclin-dependent kinases triggers mitosis. The anaphase-promoting complex is responsible for the break­down of the M cyclins and other regulators of mitosis.

Cell division is also controlled by several external fac­tors, including the presence of cytokines, various growth factors, or even adhesion factors when the cell is associated with other cells in a tissue. In addition, the cell cycle is reg­ulated by several checkpoints that determine whether DNA replication has occurred with a high degree of fidelity. Two of the better understood are the DNA damage and the spindle formation checkpoints. If these biochemical check­points are not faithfully met, the cell may default to pro­grammed cell death or apoptosis.