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Cell Cycle Phases Dividing cells are always in one of two phases: the mitotic phase or interphase. The mitotic phase (M phase) consists of mitosis and cytokinesis. Interphase consists of G1, S and G2 phases. In Figure 1 below, you can see that the mitotic phase (mitosis and cytokinesis) is relatively short compared to interphase. Cells spend approximately 90% of their time in interphase. The process of mitosis copies and distributes DNA of a cell into two identical daughter cells. Cytokinesis is the division of the cytoplasm amongst the two daughter cells. The G1 phase of interphase stands for “gap 1.” During the G1phase, the cell grows and makes proteins that are necessary for DNA replication. During the S phase, also known as the synthesis phase, the chromosomes duplicate. Therefore, the quantity of DNA in the cell at that time has doubled. During the G2 phase of interphase, the cell continues to grow and proteins are synthesized that are necessary for mitosis. During mitosis, the nucleus divides and DNA is distributed into two identical daughter cells. The cytoplasm is divided between the daughter cells through a process called cytokinesis. Each daughter cell continues through the cell cycle starting back at the G1 phase. The timing and frequency of cell division varies between different cells, tissue, organs and even species. Humans, for example, have regions where cells divide frequently such as the skin and esophagus. Conversely, in other areas of the body, such as the liver, cells can divide but only do so to repair damaged tissue. Furthermore, other cell types, such as nerve cells, never divide in a mature human. Cells that do not divide enter a phase called G0. Cell Cycle Control Systems It is necessary for cells to have checkpoints throughout the cell cycle to ensure that cells are replicating and dividing properly. If cells do not replicate and divide properly, then the growth and function of a cell may be adversely affected. For example, if the proteins that regulate cell division are not functioning properly, the result could be the replication and division of cancer cells. The cell cycle is controlled by specific signaling molecules found in the cytoplasm. These molecules verify that necessary steps in the cell cycle have been accurately completed before the cell continues to the next step of the cycle. There are three checkpoints of the cell cycle control system: G1, G2 and M. In mammals, the first and most important checkpoint is the G1 checkpoint. If a cell makes it through the G1 checkpoint, it will likely complete the subsequent stages and divide. If it does not, it will exit the cycle and remain in the G0 phase. If the conditions are right, cyclin-dependent protein kinases (Cdks) allow a cell to proceed through the G1 and G2 checkpoints. Cdks are present at constant concentrations and spend a majority of the time in an inactive form. To be active, Cdks must be attached to a cyclin. A cyclin is a protein that is present in fluctuating concentrations depending on the time of the cell cycle. Cyclin-dependent kinases require cyclin to function. Their activity level fluctuates based on the cyclin concentration in the cell. Several types of Cdk-cyclin complexes form during the cell cycle. One example is the complex called the maturation-promoting factor (MPF). MPF is formed when the cyclin level rises during the S and G2 phase, and then abruptly decreases during the M phase. MPF triggers the cell to proceed past the G2 checkpoint initiating and regulating mitosis. See Figure 8. The M checkpoint is the final checkpoint in the cell cycle. In order to pass the M checkpoint, all chromosome kinetochores must be attached to the spindle at the metaphase plate. Once attached, enzymes cause the sister chromatids to separate. This results in daughter cells with the appropriate number of chromosomes. Human Life Cycle The human life cycle begins with fertilization. When a haploid sperm from the father fuses with a haploid egg from the mother, the fusion of their nuclei is called fertilization. The fertilized egg is called a zygote. The zygote is diploid because it contains two sets of chromosomes. The zygote develops by mitosis to create all the somatic cells of the human body. See Figure 1 for an overview of the human life cycle process. The only cells that are not a result of mitosis in the human body are the gametes that develop from germ cells in the gonads. Gametes are haploid and not diploid because their offspring’s zygote must contain cells with the correct number of chromosomes. If two somatic diploid cells fused to make a zygote, those cells would each contain 92 chromosomes. This result would double the number of chromosomes present in each cell in the next generation. Meiosis reduces the number of sets of chromosomes by half in the gametes to counterbalance the doubling that occurs during fertilization. This process is essential for gamete formation. Gametes are the only haploid cells in the human body and thus contain 23 chromosomes. The human zygote has 22 pairs of autosomes and two sex chromosomes, which determine the biological sex of the offspring. A zygote with a pair of X chromosomes will be female, while a zygote with one X and one Y chromosome will be male. The Y chromosome contains the SRY gene, which controls the release of hormones. These hormones signal the development of the male during prenatal development.