One parent cell divides into two daughter cells (the word “daughter” is used customarily and does not implicate the gender of cells). In humans, one fertilized egg keeps dividing, finally forming an adult human with 60 trillion cells. After this, cell multiplication continues since the body needs to keep replenishing cells for metabolism and regeneration.
For cells to grow, a process is repeated in which cellular components, including genetic information, are doubled and distributed equally to two cells. This repetition is called the cell cycle (Fig. 9-6A). The cycle consists of the mitotic (M) phase (during which the cell is divided into two units), the synthetic (S) phase (during which DNA is synthesized), the G1 (gap 1) phase from the M phase to the S phase, and the G2 phase (gap 2) from the S phase to the M phase. The phase is a period of preparation for DNA synthesis, while the G2 phase involves preparation for cell division. In multicellular organisms, including humans, many cells stop dividing despite their ability to do so; such cells are considered to have moved out of the cell cycle and entered the G0 phase. One cell cycle in humans lasts about a day, of which the S phase takes six to eight hours to complete and the M phase takes one hour.
In eukaryotic cells, the most obvious change under the microscope is the M phase. As shown in Figure. 9-6B, nuclear division occurs following DNA synthesis, during which the nuclear envelope disappears, DNA-containing chromosomes become clearly visible and are pulled by microtubules to the two opposite ends of the cell (see Fig. 6-5 in Chapter 6). In animal cells, the plasma membrane then pinches inward to form two daughter cells, and in plant cells a dividing wall is constructed within the cell, thus forming two daughter cells.
Fig. 9-6. Cell cycle
A) The cell cycle consists of four phases - the S phase (during which DNA is synthesized), the M phase (during which the nucleus and cytoplasm are divided), and two interphases between the S and M phases. These interphases are the G1 phase from the end of the M phase to the S phase, and the G2 phase from the end of the S phase to the M phase. Many cells arrest the cell cycle during the G1 phase and enter the G0 phase.
B) In the cell cycle, only the M phase can be seen under a microscope. The remaining three phases are collectively referred to as interkinesis.
Orphan Receptors and Drug Development
Classifying the estimated 26,000 genes in the human genome by the protein families they encode, the most abundant is G protein-coupled receptors, including odorant receptors, totaling approximately 1,000 types. The second most abundant is a nuclear protein family called zinc finger proteins, totaling approximately 900 types, of which 48 are nuclear receptors.
In humans, the number of receptors involved in the detection of extracellular information is estimated to be between 2,000 and 3,000, and these are the targets of drugs. Since drugs that are effective in humans bind to receptors, these 2,000 - 3,000 receptors are basic candidate targets for drugs. Over half the superior drugs that have entered widespread use in the world target G protein-coupled receptors or nuclear receptors, and receptor-binding drugs are used to combat various diseases such as high blood pressure, stomach ulcers, lifestyle-related diseases, allergies and cancer.
However, since the human proteins that have so far been targeted by drugs number 500 types at most, there are 1,500 - 2,500 drug targets left. Receptors whose signaling molecules have not been identified are known as orphan receptors; the identification of signaling molecules for such receptors leads to the development of new medicines, prompting drug companies to scramble to find these signaling molecules.
To locate such molecules, a receptor gene whose functions are unknown is expressed in a cultured cell, and a range of chemicals is added to the culture to observe signal transduction from the receptors. In the case of G protein-coupled receptors, for example, increased Ca2+ and cAMP levels are observed as a result of the activation of G proteins. Drugs with new effects for cancer and diabetes are now being developed.
Symmetric and Asymmetric Cell Divisions
Two daughter cells produced by a cell division have the same characteristics (symmetric cell division) in many cases, but cells with different characteristics may also be formed (asymmetric cell division). As an example, one stem cell divides into two cells: one is a stem cell and the other is differentiated into a leukocyte. In this way, red and white blood cells are produced, while stem cells are preserved for later use. In the developmental process (the process during which a fertilized egg grows to become an individual), regulation by asymmetric cell division is the key to the formation of complex bodies. In this kind of cell division, the asymmetric distribution of organelles and intracellular proteins is often formed in advance (see Chapter 10).
While two daughter cells produced by asymmetric cell division have the same genes (genome), they are maintained as cells with different characteristics due to the difference in the types of genes expressed. As mentioned in Chapter 4, this difference is maintained through modification by DNA methylation, acetylation and methylation of the histone proteins constituting the chromatin structure, and other mechanisms.