9.2.

1: Cell Growth and Division

Learning Objectives
 Describe the stages of the cell cycle
 Discuss how the cell cycle is regulated
 Describe the implications of losing control over the cell cycle
 Describe the stages of mitosis and cytokinesis, in order

So far in this chapter, you have read numerous times of the importance and prevalence of cell division.
While there are a few cells in the body that do not undergo cell division (such as gametes, red blood cells,
most neurons, and some muscle cells), most somatic cells divide regularly. A somatic cell is a general term
for a body cell, and all human cells, except for the cells that produce eggs and sperm (which are referred to
as germ cells), are somatic cells. Somatic cells contain two copies of each of their chromosomes (one copy
received from each parent).

A homologous pair of chromosomes is the two copies of a single chromosome found in each somatic cell.
The human is a diploid organism, having 23 homologous pairs of chromosomes in each of the somatic
cells. The condition of having pairs of chromosomes is known as diploidy. Cells in the body replace
themselves over the lifetime of a person. For example, the cells lining the gastrointestinal tract must be
frequently replaced when constantly “worn off” by the movement of food through the gut. But what triggers
a cell to divide, and how does it prepare for and complete cell division? The cell cycle is the sequence of
events in the life of the cell from the moment it is created at the end of a previous cycle of cell division until
it then divides itself, generating two new cells.

The Cell Cycle

One “turn” or cycle of the cell cycle consists of two general phases: interphase, followed by mitosis and
cytokinesis. Interphase is the period of the cell cycle during which the cell is not dividing. The majority
of cells are in interphase most of the time. Mitosis is the division of genetic material, during which the cell
nucleus breaks down and two new, fully functional, nuclei are formed. Cytokinesis divides the cytoplasm
into two distinctive cells.

Interphase

A cell grows and carries out all normal metabolic functions and processes in a period called G 1 (Figure
1). G1 phase (gap 1 phase) is the first gap, or growth phase in the cell cycle. For cells that will divide again,
G1 is followed by replication of the DNA, during the S phase. The S phase (synthesis phase) is period
during which a cell replicates its DNA.

Figure 1. Cell Cycle. The two major phases of the cell cycle include mitosis (cell division), and interphase,
when the cell grows and performs all of its normal functions. Interphase is further subdivided into G 1, S,
and G2 phases.

After the synthesis phase, the cell proceeds through the G2 phase. The G2 phase is a second gap phase,
during which the cell continues to grow and makes the necessary preparations for mitosis. Between G 1, S,
and G2 phases, cells will vary the most in their duration of the G1 phase. It is here that a cell might spend a
couple of hours, or many days. The S phase typically lasts between 8-10 hours and the G2 phase
approximately 5 hours. In contrast to these phases, the G0 phase is a resting phase of the cell cycle. Cells
that have temporarily stopped dividing and are resting (a common condition) and cells that have
permanently ceased dividing (like nerve cells) are said to be in G0.

The Structure of Chromosomes

Figure 2. A Homologous Pair of Chromosomes with their Attached Sister Chromatids. The red and blue
colors correspond to a homologous pair of chromosomes. Each member of the pair was separately inherited
from one parent. Each chromosome in the homologous pair is also bound to an identical sister chromatid,
which is produced by DNA replication, and results in the familiar “X” shape.

Billions of cells in the human body divide every day. During the synthesis phase (S, for DNA synthesis) of
interphase, the amount of DNA within the cell precisely doubles. Therefore, after DNA replication but
before cell division, each cell actually contains two copies of each chromosome. Each copy of the
chromosome is referred to as a sister chromatid and is physically bound to the other copy.
The centromere is the structure that attaches one sister chromatid to another. Because a human cell has 46
chromosomes, during this phase, there are 92 chromatids (46 × 2) in the cell. Make sure not to confuse the
concept of a pair of chromatids (one chromosome and its exact copy attached during mitosis) and a
homologous pair of chromosomes (two paired chromosomes which were inherited separately, one from
each parent) (Figure 2).

Mitosis

The mitotic phase of the cell typically takes between 1 and 2 hours. During this phase, a cell undergoes
two major processes. First, it completes mitosis, during which the contents of the nucleus are equitably
pulled apart and distributed between its two halves. Cytokinesis then occurs, dividing the cytoplasm and
cell body into two new cells. Mitosis is divided into four major stages that take place after interphase (Table
1) and in the following order: prophase, metaphase, anaphase, and telophase. The process is then followed
by cytokinesis.
Table 1. Cell Division: Mitosis Followed by Cytokinesis

Phase Illustration Key Events

Chromosomes condense and become visible

Spindle fibers emerge from the centrosomes

Prophase
Nuclear envelope breaks down

Centrosomes move toward opposite poles

Chromosomes continue to condense

Kinetochores appear at the centromeres
Prometapha
se Mitotic spindle microtubules attach to

kinetochores
 Chromosomes are lined up at the
metaphase plate
Metaphase Each sister chromatid is attached
to a spindle fiber originating from
opposite poles

Centromeres split in two

Sister chromatids (now called chromosomes)

Anaphase
are pulled toward opposite poles

Certain spindle fibers begin to elongate the cell

 Chromosomes arrive at opposite poles and
begin to decondense
Nuclear envelope surrounds each set of

Telophase chromosomes

The mitotic spindle breaks down

Spindle fibers continue to push poles apart

 Animal cells: a cleavage furrow separates the
daughter cells
Cytokinesis
Plant cells: a cell plate, the precursor to a new
cell wall, separates the daughter cells

Prophase is the first phase of mitosis, during which the loosely packed chromatin coils and condenses into
visible chromosomes. During prophase, each chromosome becomes visible with its identical partner
attached, forming the familiar X-shape of sister chromatids. The nucleolus disappears early during this
phase, and the nuclear envelope also disintegrates. A major occurrence during prophase concerns a very
important structure that contains the origin site for microtubule growth. Recall the cellular structures called
centrioles that serve as origin points from which microtubules extend. These tiny structures also play a very
important role during mitosis. A centrosome is a pair of centrioles together. The cell contains two
centrosomes side-by-side, which begin to move apart during prophase. As the centrosomes migrate to two
different sides of the cell, microtubules begin to extend from each like long fingers from two hands
extending toward each other. The mitotic spindle is the structure composed of the centrosomes and their
emerging microtubules. Near the end of prophase there is an invasion of the nuclear area by microtubules
from the mitotic spindle. The nuclear membrane has disintegrated, and the microtubules attach themselves
to the centromeres that adjoin pairs of sister chromatids. The kinetochore is a protein structure on the
centromere that is the point of attachment between the mitotic spindle and the sister chromatids. This stage
is referred to as late prophase or “prometaphase” to indicate the transition between prophase and metaphase.

Metaphase is the second stage of mitosis. During this stage, the sister chromatids, with their attached
microtubules, line up along a linear plane in the middle of the cell. A metaphase plate forms between the
centrosomes that are now located at either end of the cell. The metaphase plate is the name for the plane
through the center of the spindle on which the sister chromatids are positioned. The microtubules are now
poised to pull apart the sister chromatids and bring one from each pair to each side of the cell.

Anaphase is the third stage of mitosis. Anaphase takes place over a few minutes, when the pairs of sister
chromatids are separated from one another, forming individual chromosomes once again. These
chromosomes are pulled to opposite ends of the cell by their kinetochores, as the microtubules shorten.
Each end of the cell receives one partner from each pair of sister chromatids, ensuring that the two new
daughter cells will contain identical genetic material.

Telophase is the final stage of mitosis. Telophase is characterized by the formation of two new daughter
nuclei at either end of the dividing cell. These newly formed nuclei surround the genetic material, which
uncoils such that the chromosomes return to loosely packed chromatin. Nucleoli also reappear within the
new nuclei, and the mitotic spindle breaks apart, each new cell receiving its own complement of DNA,
organelles, membranes, and centrioles. At this point, the cell is already beginning to split in half as
cytokinesis begins.

Cytokinesis

The cleavage furrow is a contractile band made up of microfilaments that forms around the midline of the
cell during cytokinesis. (Recall that microfilaments consist of actin.) This contractile band squeezes the two
cells apart until they finally separate. Two new cells are now formed. One of these cells (the “stem cell”)
enters its own cell cycle; able to grow and divide again at some future time. The other cell transforms into
the functional cell of the tissue, typically replacing an “old” cell there. Imagine a cell that completed mitosis
but never underwent cytokinesis. In some cases, a cell may divide its genetic material and grow in size, but
fail to undergo cytokinesis. This results in larger cells with more than one nucleus. Usually this is an
unwanted aberration and can be a sign of cancerous cells.

Cell Cycle Control

A very elaborate and precise system of regulation controls direct the way cells proceed from one phase to
the next in the cell cycle and begin mitosis. The control system involves molecules within the cell as well
as external triggers. These internal and external control triggers provide “stop” and “advance” signals for
the cell. Precise regulation of the cell cycle is critical for maintaining the health of an organism, and loss of
cell cycle control can lead to cancer.
Mechanisms of Cell Cycle Control

As the cell proceeds through its cycle, each phase involves certain processes that must be completed before
the cell should advance to the next phase. A checkpoint is a point in the cell cycle at which the cycle can
be signaled to move forward or stopped. At each of these checkpoints, different varieties of molecules
provide the stop or go signals, depending on certain conditions within the cell. A cyclin is one of the primary
classes of cell cycle control molecules (Figure 3). A cyclin-dependent kinase (CDK) is one of a group of
molecules that work together with cyclins to determine progression past cell checkpoints. By interacting
with many additional molecules, these triggers push the cell cycle forward unless prevented from doing so
by “stop” signals, if for some reason the cell is not ready. At the G1 checkpoint, the cell must be ready for
DNA synthesis to occur. At the G2 checkpoint the cell must be fully prepared for mitosis. Even during
mitosis, a crucial stop and go checkpoint in metaphase ensures that the cell is fully prepared to complete
cell division. The metaphase checkpoint ensures that all sister chromatids are properly attached to their
respective microtubules and lined up at the metaphase plate before the signal is given to separate them
during anaphase.

Figure 3.
Control of the Cell Cycle. Cells proceed through the cell cycle under the control of a variety of molecules,
such as cyclins and cyclin-dependent kinases. These control molecules determine whether or not the cell is
prepared to move into the following stage.

The Cell Cycle Out of Control: Implications

Most people understand that cancer or tumors are caused by abnormal cells that multiply continuously. If
the abnormal cells continue to divide unstopped, they can damage the tissues around them, spread to other
parts of the body, and eventually result in death. In healthy cells, the tight regulation mechanisms of the
cell cycle prevent this from happening, while failures of cell cycle control can cause unwanted and
excessive cell division. Failures of control may be caused by inherited genetic abnormalities that
compromise the function of certain “stop” and “go” signals. Environmental insult that damages DNA can
also cause dysfunction in those signals. Often, a combination of both genetic predisposition and
environmental factors lead to cancer. The process of a cell escaping its normal control system and becoming
cancerous may actually happen throughout the body quite frequently. Fortunately, certain cells of the
immune system are capable of recognizing cells that have become cancerous and destroying them.
However, in certain cases the cancerous cells remain undetected and continue to proliferate. If the resulting
tumor does not pose a threat to surrounding tissues, it is said to be benign and can usually be easily removed.
If capable of damage, the tumor is considered malignant and the patient is diagnosed with cancer.

Try It

Cancer is an extremely complex condition, capable of arising from a wide variety of genetic and
environmental causes. Typically, mutations or aberrations in a cell’s DNA that compromise normal cell
cycle control systems lead to cancerous tumors. Cell cycle control is an example of a homeostatic
mechanism that maintains proper cell function and health. While progressing through the phases of the cell
cycle, a large variety of intracellular molecules provide stop and go signals to regulate movement forward
to the next phase. These signals are maintained in an intricate balance so that the cell only proceeds to the
next phase when it is ready.

The homeostatic control of the cell cycle can be thought of like a car’s cruise control. Cruise control will
continually apply just the right amount of acceleration to maintain a desired speed, unless the driver hits
the brakes, in which case the car will slow down. Similarly, the cell includes molecular messengers, such
as cyclins, that push the cell forward in its cycle. In addition to cyclins, a class of proteins that are encoded
by genes called proto-oncogenes provide important signals that regulate the cell cycle and move it forward.
Examples of proto-oncogene products include cell-surface receptors for growth factors, or cell-signaling
molecules, two classes of molecules that can promote DNA replication and cell division.

In contrast, a second class of genes known as tumor suppressor genes sends stop signals during a cell cycle.
For example, certain protein products of tumor suppressor genes signal potential problems with the DNA
and thus stop the cell from dividing, while other proteins signal the cell to die if it is damaged beyond repair.
Some tumor suppressor proteins also signal a sufficient surrounding cellular density, which indicates that
the cell need not presently divide. The latter function is uniquely important in preventing tumor growth:
normal cells exhibit a phenomenon called “contact inhibition;” thus, extensive cellular contact with
neighboring cells causes a signal that stops further cell division.

These two contrasting classes of genes, proto-oncogenes and tumor suppressor genes, are like the
accelerator and brake pedal of the cell’s own “cruise control system,” respectively. Under normal
conditions, these stop and go signals are maintained in a homeostatic balance. Generally speaking, there
are two ways that the cell’s cruise control can lose control: a malfunctioning (overactive) accelerator, or a
malfunctioning (underactive) brake. When compromised through a mutation, or otherwise altered, proto-
oncogenes can be converted to oncogenes, which produce oncoproteins that push a cell forward in its cycle
and stimulate cell division even when it is undesirable to do so.

For example, a cell that should be programmed to self-destruct (a process called apoptosis) due to extensive
DNA damage might instead be triggered to proliferate by an oncoprotein. On the other hand, a dysfunctional
tumor suppressor gene may fail to provide the cell with a necessary stop signal, also resulting in unwanted
cell division and proliferation. A delicate homeostatic balance between the many proto-oncogenes and
tumor suppressor genes delicately controls the cell cycle and ensures that only healthy cells replicate.
Therefore, a disruption of this homeostatic balance can cause aberrant cell division and cancerous growths.