4.7 The Cell Cycle

In this section, we will cover the cell cycle in more detail.  We briefly addressed this in a previous chapter, when covering meiosis and gametogenesis.  Now, we will explore in more detail what happens to allow a single cell to divide and produce identical copies of itself, a process that is crucial for the normal development of an embryo, but that can lead to cancers if uncontrolled.

The cell cycle

The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produce two genetically identical cells. The cell cycle has two major phases: interphase and the mitotic phase (Figure 1). During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated and the cell divides.

 

This illustration shows the cell cycle, which consists of interphase and the mitotic phase. Interphase is subdivided into G1, S, and G2 phases. Cell growth occurs during G1 and G2, and DNA synthesis occurs during S. The mitotic phase consists of mitosis, in which the nuclear chromatin is divided, and cytokinesis, in which the cytoplasm is divided resulting in two daughter cells.
Figure 1. A cell moves through a series of phases in an orderly manner. During interphase, G1 involves cell growth and protein synthesis, the S phase involves DNA replication and the replication of the centrosome, and G2 involves further growth and protein synthesis. The mitotic phase follows interphase. Mitosis is nuclear division during which duplicated chromosomes are segregated and distributed into daughter nuclei. Usually the cell will divide after mitosis in a process called cytokinesis in which the cytoplasm is divided and two daughter cells are formed.

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Interphase

During interphase, the cell undergoes normal processes while also preparing for cell division. For a cell to move from interphase to the mitotic phase, many internal and external conditions must be met. The three stages of interphase are called G1, S, and G2.

G1 Phase

The first stage of interphase is called the G1 phase, or first gap, because little change is visible. However, during the G1 stage, the cell is quite active at the biochemical level. The cell is accumulating the building blocks of chromosomal DNA and the associated proteins, as well as accumulating enough energy reserves to complete the task of replicating each chromosome in the nucleus.

S Phase

Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration. In the S phase (synthesis phase), DNA replication results in the formation of two identical copies of each chromosome—sister chromatids—that are firmly attached at the centromere region. At this stage, each chromosome is made of two sister chromatids and is a duplicated chromosome. The centrosome is duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. The centrosome consists of a pair of rod-like centrioles at right angles to each other. Centrioles help organize cell division. Centrioles are not present in the centrosomes of many eukaryotic species, such as plants and most fungi.

G2 Phase

In the G2 phase, or second gap, the cell replenishes its energy stores and synthesizes the proteins necessary for chromosome manipulation. Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic spindle. There may be additional cell growth during G2. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis.

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The Mitotic Phase

To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells.

Mitosis

Mitosis is divided into a series of phases—prophase, prometaphase, metaphase, anaphase, and telophase—that result in the division of the cell nucleus (Figure 2). The processes that occur during each of these phases, and microscope images of cells in each phase are shown below for your reference, but YOU DO NOT NEED TO MEMORIZE THEM FOR THE EXAM.

 

ART CONNECTION

 

This diagram shows the five phases of mitosis, and cytokinesis. During prophase, the chromosomes condense and become visible, spindle fibers emerge from the centrosomes, the centrosomes move toward opposite poles, and the nuclear envelope breaks down. During prometaphase, the chromosomes continue to condense and kinetochores appear at the centromeres. Mitotic spindle microtubules attach to the kinetochores. During metaphase, the centrosomes are at opposite poles of the cell. Chromosomes line up at the metaphase plate and each sister chromatid is attached to spindle fibers originating from the opposite poles. During anaphase, the centromeres split in two. The sister chromatids, which are now called chromosomes, move toward opposite poles of the cell. Certain spindle fibers lengthen, elongating the cell. During telophase, the chromosomes arrive at the opposite poles and begin to decondense. The nuclear envelope re-forms. During cytokinesis in animals, a cleavage furrow separates the two daughter cells. In plants, a cell plate—the precursor to a new cell wall—separates the two daughter cells.
Figure 2. Animal cell mitosis is divided into five stages—prophase, prometaphase, metaphase, anaphase, and telophase—visualized here by light microscopy with fluorescence. Mitosis is usually accompanied by cytokinesis, shown here by a transmission electron microscope. (credit “diagrams”: modification of work by Mariana Ruiz Villareal; credit “mitosis micrographs”: modification of work by Roy van Heesbeen; credit “cytokinesis micrograph”: modification of work by the Wadsworth Center, NY State Department of Health; donated to the Wikimedia foundation; scale-bar data from Matt Russell)

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G0 Phase

Not all cells adhere to the classic cell-cycle pattern in which a newly formed daughter cell immediately enters interphase, closely followed by the mitotic phase. Cells in the G0 phase are not actively preparing to divide. The cell is in a quiescent (inactive) stage, having exited the cell cycle. Some cells enter G0 temporarily until an external signal triggers the onset of G1. Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells, remain in G0 permanently (Figure 3).

 

The cell cycle is shown in a circular graphic, with four stages. The S stage accounts for about 40 percent of the cycle. The G2 stage accounts for about 19 percent. Mitosis accounts for 2 percent, and G1 accounts for 39 percent. An arrow is shown exiting the G1 stage that points to the G0 stage outside the circle, in which cells are not actively dividing. Another arrow points from the G0 stage back into the G1 stage, where cells may re-enter the cycle.
Figure 3. Cells that are not actively preparing to divide enter an alternate phase called G0. In some cases, this is a temporary condition until triggered to enter G1. In other cases, the cell will remain in G0 permanently.

 

Control of the Cell Cycle

The length of the cell cycle is highly variable even within the cells of an individual organism. In humans, the frequency of cell turnover ranges from a few hours in early embryonic development to an average of two to five days for epithelial cells, or to an entire human lifetime spent in G0 by specialized cells such as cortical neurons or cardiac muscle cells. There is also variation in the time that a cell spends in each phase of the cell cycle. When fast-dividing mammalian cells are grown in culture (outside the body under optimal growing conditions), the length of the cycle is approximately 24 hours. In rapidly dividing human cells with a 24-hour cell cycle, the G1 phase lasts approximately 11 hours. The timing of events in the cell cycle is controlled by mechanisms that are both internal and external to the cell.

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Regulation at Internal Checkpoints

It is essential that daughter cells be exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from the abnormal cell. To prevent a compromised cell from continuing to divide, there are internal control mechanisms that operate at three main cell cycle checkpoints at which the cell cycle can be stopped until conditions are favorable. These checkpoints occur near the end of G1, at the G2–M transition, and during metaphase (Figure 4).

 

This illustration shows the three major check points of the cell cycle, which occur in G1, G2, and mitosis.
Figure 4. The cell cycle is controlled at three checkpoints. Integrity of the DNA is assessed at the G1 checkpoint. Proper chromosome duplication is assessed at the G2 checkpoint. Attachment of each kinetochore to a spindle fiber is assessed at the M checkpoint.

 

The G1 Checkpoint

The G1 checkpoint determines whether all conditions are favorable for cell division to proceed. The G1 checkpoint, also called the restriction point, is the point at which the cell irreversibly commits to the cell-division process. In addition to adequate reserves and cell size, there is a check for damage to the genomic DNA at the G1 checkpoint. A cell that does not meet all the requirements will not be released into the S phase.

The G2 Checkpoint

The G2 checkpoint bars the entry to the mitotic phase if certain conditions are not met. As in the G1 checkpoint, cell size and protein reserves are assessed. However, the most important role of the G2 checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged.

The M Checkpoint

The M checkpoint occurs near the end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle checkpoint because it determines if all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to spindle fibers arising from opposite poles of the cell.

 

Concept in Action

Watch what occurs at the G1, G2, and M checkpoints by visiting this animation of the cell cycle.

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Section Summary

The cell cycle is an orderly sequence of events. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages. In eukaryotes, the cell cycle consists of a long preparatory period, called interphase. Interphase is divided into G1, S, and G2 phases. Mitosis and cytokinesis are the steps during which the cell divides into two daughter cells.

Each step of the cell cycle is monitored by internal controls called checkpoints. There are three major checkpoints in the cell cycle: one near the end of G1, a second at the G2–M transition, and the third during metaphase.

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Glossary

anaphase
the stage of mitosis during which sister chromatids are separated from each other
cell cycle
the ordered sequence of events that a cell passes through between one cell division and the next
cell cycle checkpoints
mechanisms that monitor the preparedness of a eukaryotic cell to advance through the various cell cycle stages
cytokinesis
the division of the cytoplasm following mitosis to form two daughter cells
G0 phase
a cell-cycle phase distinct from the G1 phase of interphase; a cell in G0 is not preparing to divide
G1 phase
(also, first gap) a cell-cycle phase; first phase of interphase centered on cell growth during mitosis
G2 phase
(also, second gap) a cell-cycle phase; third phase of interphase where the cell undergoes the final preparations for mitosis
interphase
the period of the cell cycle leading up to mitosis; includes G1, S, and G2 phases; the interim between two consecutive cell divisions
metaphase
the stage of mitosis during which chromosomes are lined up at the metaphase plate
mitosis
the period of the cell cycle at which the duplicated chromosomes are separated into identical nuclei; includes prophase, prometaphase, metaphase, anaphase, and telophase
mitotic phase
the period of the cell cycle when duplicated chromosomes are distributed into two nuclei and the cytoplasmic contents are divided; includes mitosis and cytokinesis
mitotic spindle
the microtubule apparatus that orchestrates the movement of chromosomes during mitosis
prophase
the stage of mitosis during which chromosomes condense and the mitotic spindle begins to form
quiescent
describes a cell that is performing normal cell functions and has not initiated preparations for cell division
S phase
the second, or synthesis phase, of interphase during which DNA replication occurs
telophase
the stage of mitosis during which chromosomes arrive at opposite poles, decondense, and are surrounded by new nuclear envelopes

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