 Renewing cell populations may be slowly or rapidly renewing but display regular mitotic activity. Division of such cells usually results in two daughter cells that differentiate both morphologically and functionally or two cells that remain as stem cells. Daughter cells may divide one or more times before their mature state is reached. The differentiated cell may ultimately be lost from the body.
 Slowly renewing populations include smooth muscle cells of most hollow organs, fibroblasts of the uterine wall, and epithelial cells of the lens of the eye. Slowly renewing populations may actually slowly increase in size during life, as do the smooth muscle cells of the gastrointestinal tract and the epithelial cells of the lens.
 Rapidly renewing populations include blood cells, epithelial cells and dermal fibroblasts of the skin, and the epithelial cells and subepithelial fibroblasts of the mucosal lining of the alimentary tract.
Phases and Checkpoints Within the Cell Cycle
The cell cycle represents a self-regulated sequence of events that controls cell growth and cell division.
For renewing cell populations and growing cell populations, including embryonic cells, and cells in tissue culture, the goal of the cell cycle is to produce two daughter cells, each containing chromosomes identical to those of the parental cell. The cell cycle incorporates two principal phases: the interphase, representing continuous growth of the cell, and the M phase (mitosis), characterized by the partition of the genome. Three other phases, G1 (gap1) phase, S (synthesis) phase, and G2 (gap2) phase, further subdivide interphase (Fig. 3.10). Rapidly renewing populations of human cells progress through the full cell cycle in about 24 hours. Throughout the cycle, several internal quality-control mechanisms or checkpoints represented by biochemical pathways control transition between cell-cycle stages. The cell cycle stops at several checkpoints and can only proceed if certain conditions are met—for example, if the cell has reached a certain size. Checkpoints monitor and modulate the progression of cells through the cell cycle in response to intracellular or environmental signals.
The G1 phase is usually the longest and the most variable phase of the cell cycle, and it begins at the end of M phase.
During the G1 phase, the cell gathers nutrients and synthesizes RNA and proteins necessary for DNA synthesis and 912 h 7.510 h 3.54.5 h 1 h G1 GO GTD S G2 M G1 DNA-damage checkpoint G2 DNA-damage checkpoint S DNA-damage checkpoint unreplicated DNA checkpoint checkpoint checkpoint restriction checkpoint
FIGURE 3.10 • Cell cycle and checkpoints. This diagram illustrates the cell cycle of rapidly dividing cells in relation to DNA synthesis. After mitosis, the cell is in interphase. G1 represents the period during which a gap occurs in DNA synthesis. S represents the period during which DNA synthesis occurs. G2 represents a second gap in DNA synthesis. GO represents the path of a cell that has stopped dividing; however, such a cell may reenter the cell cycle after an appropriate stimulus. The cell residing in GO may undergo terminal differentiation, GTD, and produce a population of permanent nondividing cells (e.g., mature fat cells). The average timing of each phase of the cell cycle is indicated on the diagram. Each phase contains several checkpoints that ensure that the system only proceeds to the next stage when the previous stage has been completed and no damage to the DNA is detected.
chromosome replication. The cell’s progress through this phase is monitored by two checkpoints: (1) the restriction point, which is sensitive to the size of the cell, the state of the cell’s physiologic processes, and its interactions with extracellular matrix; and (2) the G1 DNA-damage checkpoint, which monitors the integrity of newly replicated DNA. For instance, if the DNA has irreparable damage, then the G1 DNA-damage checkpoint detects the high levels of tumor-suppressing protein p53 and it does not allow the cell to enter the S phase. The cell will then most likely undergo programmed cell death (apoptosis).