Samantha Fowler; Rebecca Roush; James Wise

Learning Objectives

By the end of this section, you will be able to:

Describe the three stages of interphase
Discuss the behavior of chromosomes during mitosis and how the cytoplasmic content divides during cytokinesis
Define the quiescent G₀ phase
Explain how the three internal control checkpoints occur at the end of G₁, at the G₂–M transition, and during metaphase

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 6.3). 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. Watch this video about the cell cycle: https://openstax.org/l/biocellcyc

Figure 6.3 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.

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.

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 6.4).

Visual 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 6.4 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)

Which of the following is the correct order of events in mitosis?

Sister chromatids line up at the metaphase plate. The kinetochore becomes attached to the mitotic spindle. The nucleus re-forms and the cell divides. The sister chromatids separate.
The kinetochore becomes attached to the mitotic spindle. The sister chromatids separate. Sister chromatids line up at the metaphase plate. The nucleus re-forms and the cell divides.
The kinetochore becomes attached to metaphase plate. Sister chromatids line up at the metaphase plate. The kinetochore breaks down and the sister chromatids separate. The nucleus re-forms and the cell divides.
The kinetochore becomes attached to the mitotic spindle. Sister chromatids line up at the metaphase plate. The kinetochore breaks apart and the sister chromatids separate. The nucleus re-forms and the cell divides.

During prophase, the “first phase,” several events must occur to provide access to the chromosomes in the nucleus. The nuclear envelope starts to break into small vesicles, and the Golgi apparatus and endoplasmic reticulum fragment and disperse to the periphery of the cell. The nucleolus disappears. The centrosomes begin to move to opposite poles of the cell. The microtubules that form the basis of the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly and become visible under a light microscope.

During prometaphase, many processes that were begun in prophase continue to advance and culminate in the formation of a connection between the chromosomes and cytoskeleton. The remnants of the nuclear envelope disappear. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and visually discrete. Each sister chromatid attaches to spindle microtubules at the centromere via a protein complex called the kinetochore.

During metaphase, all of the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other. At this time, the chromosomes are maximally condensed.

During anaphase, the sister chromatids at the equatorial plane are split apart at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule was attached. The cell becomes visibly elongated as the non-kinetochore microtubules slide against each other at the metaphase plate where they overlap.

During telophase, all of the events that set up the duplicated chromosomes for mitosis during the first three phases are reversed. The chromosomes reach the opposite poles and begin to decondense (unravel). The mitotic spindles are broken down into monomers that will be used to assemble cytoskeleton components for each daughter cell. Nuclear envelopes form around chromosomes.

Link to Learning

This page of movies illustrates different aspects of mitosis. Watch the movie entitled “DIC microscopy of cell division in a newt lung cell” and identify the phases of mitosis.

Cytokinesis

Cytokinesis is the second part of the mitotic phase during which cell division is completed by the physical separation of the cytoplasmic components into two daughter cells. Although the stages of mitosis are similar for most eukaryotes, the process of cytokinesis is quite different for eukaryotes that have cell walls, such as plant cells.

In cells such as animal cells that lack cell walls, cytokinesis begins following the onset of anaphase. A contractile ring composed of actin filaments forms just inside the plasma membrane at the former metaphase plate. The actin filaments pull the equator of the cell inward, forming a fissure. This fissure, or “crack,” is called the cleavage furrow. The furrow deepens as the actin ring contracts, and eventually the membrane and cell are cleaved in two (Figure 6.5).

In plant cells, a cleavage furrow is not possible because of the rigid cell walls surrounding the plasma membrane. A new cell wall must form between the daughter cells. During interphase, the Golgi apparatus accumulates enzymes, structural proteins, and glucose molecules prior to breaking up into vesicles and dispersing throughout the dividing cell. During telophase, these Golgi vesicles move on microtubules to collect at the metaphase plate. There, the vesicles fuse from the center toward the cell walls; this structure is called a cell plate. As more vesicles fuse, the cell plate enlarges until it merges with the cell wall at the periphery of the cell. Enzymes use the glucose that has accumulated between the membrane layers to build a new cell wall of cellulose. The Golgi membranes become the plasma membrane on either side of the new cell wall (Figure 6.5).

This illustration shows cytokinesis in a typical animal cell and a typical plant cell. In an animal cell, a contractile ring of actin filaments forms a cleavage furrow that divides the cell in two. In a plant cell, Golgi vesicles coalesce at the metaphase plate. A cell plate grows from the center outward, and the vesicles form a plasma membrane that divides the cytoplasm.

Figure 6.5 In part (a), a cleavage furrow forms at the former metaphase plate in the animal cell. The plasma membrane is drawn in by a ring of actin fibers contracting just inside the membrane. The cleavage furrow deepens until the cells are pinched in two. In part (b), Golgi vesicles coalesce at the former metaphase plate in a plant cell. The vesicles fuse and form the cell plate. The cell plate grows from the center toward the cell walls. New cell walls are made from the vesicle contents.

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 6.6).

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 6.6 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.

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 6.7).

This illustration shows the three major check points of the cell cycle, which occur in G1, G2, and mitosis.

Figure 6.7 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.

Link to Learning

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

6.2 The Cell Cycle