Mitosis

Mitosis, process in which a cell’s nucleus replicates and divides in preparation for division of the cell. Mitosis results in two cells that are genetically identical, a necessary condition for the normal functioning of virtually all cells. Mitosis is vital for growth; for repair and replacement of damaged or worn out cells; and for asexual reproduction, or reproduction without eggs and sperm.

All multicellular animals, plants, fungi, and protists, which begin life as single cells, carry out mitosis to develop into complex organisms containing billions of cells. Mitosis continues in full-grown organisms as a means of maintaining the organism—replacing dying skin cells, for example, or repairing damaged muscle cells. In the cells of the adult human body, mitosis occurs about 25 million times per second. Multicellular organisms such as sea stars, sea anemones, fungi, and certain plants rely on mitosis for asexual reproduction at particular stages in their life cycles, and mitosis is the sole mode of reproduction for many single-celled organisms.

INTERPHASE

The life cycle of eukaryotic cells, or cells containing a nucleus, is a continuous process typically divided into three phases for ease of understanding: interphase, mitosis, and cytokinesis. Interphase includes three stages, referred to as G₁, S and G₂. In G₁, a newly formed cell synthesizes materials needed for cell growth. In the S stage, deoxyribonucleic acid (DNA), the genetic material of the cell, is replicated. At this stage, DNA consists of long, thin strands called chromatin. As each strand is replicated, it is linked to its duplicate by a structure known as a centromere. When the S stage is complete, the cell enters a brief stage known as G_2, when specialized enzymes correct any errors in the newly synthesized DNA, and proteins involved with the next phase, mitosis, are synthesized.

MITOSIS

Mitosis occurs in five steps: prophase, prometaphase, metaphase, anaphase, and telophase . In prophase the replicated, linked DNA strands slowly wrap around proteins that in turn coil and condense into two short, thick, rodlike structures called chromatids, attached by the centromere. Two structures called centrioles, both located on one side of the nucleus, separate and move toward opposite poles of the cell. As the centrioles move apart, they begin to radiate thin, hollow, proteins called microtubules. The microtubules arrange themselves in the shape of a football, or spindle, that spans the cell, with the widest part at the center of the cell and the narrower ends at opposite poles.

Prometaphase is marked by the disintegration of the nuclear membrane. As the spindle forms, the nuclear membrane breaks down into tiny sacs or vesicles that are dispersed in the cytoplasm. The spindle fibers attach to the chromatids near the centromeres, and tug and push the chromatids so that they line up in the equatorial plane of the cell halfway between the poles. Like two individuals standing back to back at the equator, one chromatid faces one pole of the cell, and its linked partner faces the opposite pole.

In metaphase, exactly half of the chromatids face one pole, and the other half face the other pole. This equilibrium position is called the metaphase plate.

Anaphase begins when the centromeres split, separating the identical chromatids into single chromosomes, which then move along the spindle fibers to opposite poles of the cell. At the end of anaphase, two identical groups of single chromosomes congregate at opposite poles of the cell.

In telophase, the final stage of mitosis, a new nuclear membrane forms around each new group of chromosomes. The spindle fibers break down and the newly formed chromosomes begin to unwind. If viewed under a light microscope, the chromosomes appear to fade away. They exist, however, in the form of chromatin, the extended, thin strands of DNA too fine to be seen except with electron microscopes. Mitosis accomplishes replication and division of the nucleus, but the cell has yet to divide.

CYTOKINESIS

The final phase of the cell cycle is known as cytokinesis. The timing of cytokinesis varies depending on the cell type. It can begin in anaphase and finish in telophase; or it can follow telophase. In cytokinesis, the cell’s cytoplasm separates in half, with each half containing one nucleus. Animals and plants accomplish cytokinesis in slightly different ways. In animals, the cell membrane pinches in, creating a cleavage furrow, until the mother cell is pinched in half. In plants, cellulose and other materials that make up the cell wall are transported to the midline of the cell and a new cell wall is constructed. The process of DNA replication, the precise alignment of the chromosomes in mitosis, and the successful separation of identical chromatids in anaphase results in two new cells that are genetically identical. The new cells enter interphase, and the cell cycle begins again.

CONTROL OF CELL DIVISION

In multicellular organisms, cell division must be carefully regulated to ensure that growth of the organism is coordinated, replacement of dead cells takes place in an orderly fashion, and repair of injured cells is initiated when needed. Cell division must also be halted when growth and repair are completed. Cell division is controlled by a variety of factors. One of the most important controls is carried out by molecules called growth factors.

Growth factors first come into play late in the G₁stage of interphase. Cells cannot pass from G₁ to the S stage unless growth factors bind to the plasma membrane. The binding of growth factors triggers a cascade of biochemical activity that propels the cell into the S stage. If the cell does not enter the S stage, it exits from the cell cycle into the G₀ stage, a period of normal metabolic activity where other control mechanisms prevent it from dividing. Most of the cells in the adult human body remain in the G₀ stage throughout life. Certain cells, such as bone, muscle, or liver cells, can return to the cell cycle and divide if they are injured. Injuries release growth factors that override the controls over the non-dividing state.

Once a cell is committed to dividing, still other growth factors ensure that steps in mitosis are carried out accurately. At the end of the G₂ stage, mitotic (or maturation) promoting factor (MPF) triggers prophase, and enzymes condense DNA into chromosomes, break down the nuclear membrane, and form the spindle. A complex interplay of other growth factors carries the cell through the remaining steps of mitosis and cytokinesis.

Scientists have identified over 50 different growth factors. Some are very specific, and react only with certain cells. Nerve growth factor, for example, stimulates the growth of nerve cells during embryonic development, but has no effect on other cells. Others, such as epidermal growth factor, control division in a variety of cells. Understanding the production of growth factors and their precise mode of activity pose significant research challenges. As scientists learn more about the mechanisms for normal cell division, they gain insight into the causes of the unregulated cell growth that leads to cancer.