Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Nucleic Acids and Genes
Cell Cycle

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Fig. 29.1. Cell cycle.

The Cell cycle is The sequence of events occurring during Cell Division that results in The formation of two daughter Cells. The elements of the cell cycle in Prokaryotic Cells have not yet been fully characterized. In contrast, for eukaryotes, the set of cellular events is clearly established: the order of these events within the cycle is fixed, but the duration can vary considerably.

Prokaryotic Cell DIVISION involves the Replication of a single circular chromosome and all Plasmids contained within the cell, as well as the duplication of cellular Organelles, including The Plasma Membrane and Cell wall components. The rate of bacterial division depends on the nutrient availability in the growth medium. If any essential substrates are lacking, the rate of replication initiation decreases, while the rate of replication itself remains unchanged.

The duration of replication in most prokaryotic cells is surprisingly constant (about 40 min). Once DNA duplication has begun, it proceeds to completion regardless of any changes in nutrient medium composition occurring during this time. The period preceding the initiation of METABOLISM/36.html">DNA replication is variable (20–220 min). The two Examples in Fig. 29.1 separately illustrate long and short cycles. A long cycle occurs when the time preceding initiation is long; in this case, once replication has started, no new initiation sites arise on the chromosome until all events of the cell cycle are completed. The time required for new initiation sites to appear is variable, and it is the primary factor determining the total duration of the cell cycle. A short cycle occurs when new initiation sites appear before the replication cycle is fully complete. Thus, the next replication cycle begins even before cell division is finished.

The initiation of replication is mediated by specific Proteins. If cells are placed in a medium lacking a key substrate, such as Tryptophan, Protein Synthesis stops immediately. Although DNA Replication and cell division continue, a new replication cycle does not begin until protein synthesis resumes. It follows that initiators are proteins that interact with DNA and convert it into a state capable of binding DNA polymerase.

Cell division occurs when the total cell mass is sufficient for two cells and when replication is complete. The time required for the division process is relatively constant, taking about 20 min.

EUKARYOTIC MITOTIC CELL DIVISION encompasses a series of cell cycle phases that collectively may take about 24 hours for a single division cycle.

Interphase corresponds to the segment of the cycle during which nuclear Chromatin is dispersed throughout The Nucleus and no visible signs of Chromosomes can be detected. Interphase is subdivided into four periods: G_o, G₁, S, and G₂.

Prophase follows interphase and is the period following G₂ when condensed chromosomes become distinguishable.

Mitosis (M) is the period following prophase during which chromosome reorganization takes place, culminating in the formation of two nuclei and, ultimately, two daughter cells. Three distinct subperiods of mitosis are recognized: metaphase, anaphase, and telophase.

The G_o phase is variable in duration. A cell may transition into it immediately after division. A cell in the G_o phase is referred to as quiescent, i.e., in a non-dividing state. Cells in many adult Tissues reside predominantly in this state: they do not undergo DNA replication and may exhibit only very low levels of RNA Synthesis. The transition of a cell into the G_o phase is influenced by factors such as nutrient depletion, intercellular contact inhibition of division, and intracellular regulators (e.g., cyclic AMP under certain conditions). When a cell in the G_o phase is exposed to specific Hormones and other growth factors, it can transition from G_o to G₁.

The G₁ phase is the period during which the cell prepares for the onset of DNA Synthesis, which takes place in the S phase. The duration of G₁ is variable (ranging from several hours to a day or even longer). The reason for this is unknown, but adding hormones to cells in G₁ often shortens the duration of this phase. This can be explained by an increase in the synthesis rate of certain key molecules driven by hormones. Frequently, a hormone must be present within or on the cell surface for at least 8 hours before DNA replication can begin. The reason for this phenomenon remains unknown. By the end of G₁, the cell is fully prepared to enter the S phase.

The S phase is the period during which The amount of DNA doubles, preceding the division of the cell into two daughters. The duration of the S phase varies only slightly from Cell to Cell, lasting about 6–8 hours. DNA replication can be monitored during this period by measuring the incorporation rate of tritium-labeled thymidine (³H-T) into DNA. Concurrently, RNA synthesis takes place. If ³H-cytidine is added to cells in the S phase, radioactive RNA appears first in the nucleus and then in the Cytoplasm. Although RNA is synthesized throughout interphase, this process reaches its peak intensity during the S phase. Cells can be arrested in the S phase by adding inhibitors such as actinomycin D, which blocks RNA polymerase activity by intercalating into DNA (Ch. 43). In this case, the cell cycle cannot proceed until DNA replication is complete. Upon completion of nucleic acid synthesis and the doubling of most other cellular components, the cell transitions into the G₂ phase.

The G₂ phase is the segment of interphase during which DNA replication does not occur and only very low levels of RNA synthesis may take place; i.e., G₂ is an intermediary period. In the G₂ phase, the chromosome content of the cell is twice that of a normal diploid cell. The duration of the G₂ phase is approximately 2–6 hours and depends relatively little on the cell type. During G₂, chromatin Condensation occurs and the nuclear envelope breaks down. Between G₂ and M, the cell passes through prophase.

In prophase, highly condensed chromosomes are actually seen to consist of two intertwined yet separate structures called chromatids. Each chromatid is a complete copy of double-stranded DNA complexed with proteins. During prophase, the centrioles, which previously divided to form smaller daughter centrioles, migrate to opposite poles. A complex bundle of microtubules (Ch. 39) emerging from the centrioles is visible, known as the mitotic spindle. It is formed by microtubules positioned between the centrioles and has an egg-like shape. This Structure acts as a cellular scaffold. As the cell enters mitosis, chromosomes associate with this scaffold, and the nuclear envelope is no longer visible. Chromosomes attach to the microtubules via their centromeres. Mitosis (M) is subdivided into three periods: metaphase, anaphase, and telophase.

In metaphase, chromosomes align across the mitotic spindle, forming the metaphase plate. The mechanism underlying this orientation remains unknown.

In anaphase, chromosomes split into their constituent chromatids. Each chromatid of every pair moves toward one or the other pole of the mitotic spindle. The movement of the chromatids, now referred to as daughter chromosomes, is driven by the shortening of microtubules, although the detailed mechanism of this process is unknown. Upon completion of chromatid Separation, the cell enters telophase.

In telophase, chromatids decondense to form dispersed chromatin, and nuclear envelopes reform. The mitotic spindle disassembles, and the plasma membrane pinches inward. As a result, two daughter cells are produced. Each daughter cell then enters a new cell cycle in either the G_o or G₁ phase, and the entire process repeats.