The Cell Cycle Is an Ordered Series of Events Leading to Cell Replication

The cell cycle is divided into four major phases (see Figure 19-1). Cycling (replicating) mammalian somatic cells grow in size and synthesize the RNAs and proteins required for DNA synthesis during the G₁ (first gap) phase. When cells have reached the appropriate size and have synthesized the required proteins, they enter the cell cycle by traversing a point in G₁ known as START in yeast and the restriction point in mammals. Once this point has been crossed, cells are committed to cell division. The first step toward successful cell division is entry into the S (synthesis) phase, the period in which cells actively replicate their chromosomes. After progressing through a second gap phase, the G₂ phase, cells begin the complicated process of mitosis, also called the M (mitotic) phase, which is divided into several stages (Figure 19-2).

In discussing mitosis, we commonly use the term chromosome for the replicated structures that condense and become visible in the light microscope during the early stages of mitosis. Thus each chromosome is composed of two identical DNA molecules resulting from DNA replication, plus histones and other chromosome-associated proteins (see Figure 8-35). The two identical DNA molecules and associated chromosomal proteins that form one chromosome are called sister chromatids. Sister chromatids are attached to each other by protein cross-links.

During interphase, the part of the cell cycle between the end of one M phase and the beginning of the next, the outer nuclear membrane is continuous with the endoplasmic reticulum. With the onset of mitosis in prophase, the nuclear envelope retracts into the endoplasmic reticulum in most cells from higher eukaryotes, and the membranes of the Golgi complex break down into vesicles. This is necessary so that the microtubules, nucleated by the centrosomes, can interact with the chromosomes to form the mitotic spindle, consisting of a football-shaped bundle of microtubules with a star-shaped cluster of microtubules radiating from each end, or spindle pole. A multiprotein complex, the kinetochore, assembles at each centromere. After nuclear envelope breakdown, at metaphase, the kinetochores of sister chromatids associate with microtubules coming from opposite spindle poles (see Figure 18-37), and the chromosomes align in a plane in the center of the cell. During anaphase, sister chromatids separate. They are initially pulled by microtubules toward the spindle poles and are then further separated as the spindle poles move away from each other (see Figure 19-2).

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Once chromosome separation is complete, the mitotic spindle disassembles and chromosomes decondense during telophase. The nuclear envelope re-forms around the segregated chromosomes as they decondense. The physical division of the cytoplasm, called cytokinesis, yields two daughter cells. Following mitosis, cycling cells enter the G₁ phase, embarking on another turn of the cycle.

The progression of cell cycle stages is the same for all eukaryotes, though the time it takes to complete one turn of the cycle varies considerably among organisms. Rapidly replicating human cells progress through the full cell cycle in about 24 hours: G₁ takes 9 hours; the S phase, 10 hours; G₂, 4.5 hours; and mitosis, 30 minutes. In contrast, the full cycle takes only 90 minutes in rapidly growing yeast cells. The cell divisions that take place during early embryonic development of the fruit fly Drosophila melanogaster are completed in as little as 8 minutes!

In multicellular organisms, most differentiated cells exit the cell cycle and survive for days, weeks, or in some cases (e.g., nerve cells and cells of the eye lens) even the lifetime of the organism without dividing again. Such postmitotic cells generally exit the cell cycle in G₁, entering a phase called G₀ (see Figure 19-1). Some G₀ cells can return to the cell cycle and resume replicating; this re-entry is regulated, thereby providing control of cell proliferation.