Red blood cells, striated muscle cells, uterine smooth muscle cells, and nerve cells are terminally differentiated. Other cells, such as fibroblasts, exit from the G1 phase into the G0 phase and are considered to be out of the cell cycle. These cells enter the cell cycle following exposure to specific stimuli, such as growth factors and steroid hormones. Dividing cells are found in the gastrointestinal tract, the skin, and the cervix.
G1 Phase In response to specific external stimuli, cells enter the cell cycle by moving from the G0 phase into the G1 phase. The processes during G1 phase lead to the synthesis of enzymes and regulatory proteins necessary for DNA synthesis during S phase and are mainly regulated by G1 cyclindependent kinase–cyclin complexes (G1CdkC). Complexes of G1CdkC induce degradation of the S phase inhibitors in late G1. Release of the S phase CdkC complex subsequently stimulates entry into the S phase. Variations in the duration of the G1 phase of the cell cycle, ranging from less than 8 hours to longer than 100 hours, account for the different generation times exhibited by different types of cells.
S Phase The nuclear DNA content of the cell is duplicated during the S phase of the cell cycle. The S phase CdkC complex activates proteins of the DNA prereplication complexes that assemble on DNA replication origins during G1. The prereplication complex activates initiation of DNA replication and inhibits the assembly of new prereplication complexes. This inhibition ascertains that each chromosome is replicated only once during the S phase.
G2 Phase RNA and protein synthesis occurs during the G2 phase of the cell cycle. The burst of biosynthetic activity provides the substrates and enzymes to meet the metabolic requirements of the two daughter cells. Another important event that occurs during the G2 phase of the cell cycle is the repair of errors of DNA replication that may have occurred during the S phase. Failure to detect and correct these genetic errors can result in a broad spectrum of adverse consequences for the organism and the individual cell (1). Defects in the DNA repair mechanism are associated with an increased incidence of cancer (2). Mitotic CdkC complexes are synthesized during the S and G2 phases, but are inactive until DNA synthesis is completed.
M Phase Nuclear–chromosomal division occurs during the mitosis or M phase. During this phase, the cellular DNA is equally distributed to each of the daughter cells. Mitosis provides a diploid (2n) DNA complement to each somatic daughter cell. Following mitosis, eukaryotic mammalian cells contain diploid DNA, reﬂecting a karyotype that includes 44 somatic chromosomes and an XX or XY sex chromosome complement. Exceptions to the diploid cellular content include hepatocytes (4n) and the functional syncytium of the placenta.
Mitosis is divided into prophase, metaphase, anaphase, and telophase. Mitotic CdkC complexes induce chromosome condensation during the prophase, assembly of the mitotic spindle apparatus, and alignment of the chromosomes during the metaphase. Activation of the anaphase promoting complex (APC) leads to inactivation of the protein complexes that connect sister chromatids during metaphase, permitting the onset of anaphase. During anaphase, sister chromatids segregate to opposite spindle poles. The nuclear envelope breaks down into multiple small vesicles early in mitosis and reforms around the segregated chromosomes as they decondense during telophase. Cytokinesis is the process of division of the cytoplasm that segregates the endoplasmic reticulum and the Golgi apparatus during mitosis. After completion of mitosis, cells enter the G1 phase and either re-enter the cell cycle or remain in G0.