The Cell Cycle

The cell cycle is composed of three main stages: Interphase, mitosis and cytokinesis. Interphase is the
longest phase of the cell cycle. In a 24-hour cycle, a cell only spends about one hour in mitosis and cytokinesis, and
the rest is spent in interphase. Mitosis is the division of the nucleus, which is initiated after the completion
interphase. Mitosis results in cytokinesis, which occurs when the cytoplasm from the original cell divides and
forms two new cells.

Regulating the Cell Cycle

The Discovery of Cyclins

In the early 1980s, biologists were able to elucidate studies on sea urchins the proteins in cells that are
responsible for regulating the cell cycle. They named this protein cyclin. Biologists were able to identify more
members of the cyclin family of proteins which are responsible for regulating the cell cycle.
Cyclins are regulatory subunits of the kinases involved in the eukaryotic cell cycle. Cyclins are proteins
whose concentration in the cells increases and decreases in phase with the cell cycle. Passage through the cycle is
controlled by cyclin-dependent kinase complexes which are inactive unless associated with a cyclin.

Regulatory Proteins
Aside from the cyclin family, scientists have discovered other proteins that help regulate cell cycle. The cell
cycle is regulated by both internal and external regulators.

 Internal regulators are proteins found inside the cell. They regulate the processes that happen inside the
cell. Internal regulatory proteins include the proteins that make sure that mitosis does not occur unless the
chromosomes have replicated. Another example is the protein that prevents the cells from entering
anaphase unless the spindle fibers have already attached themselves to the chromosomes.
  External regulators are proteins that respond to events outside the cell. One of the important external
regulators is the growth factors that stimulate the growth and division of cells. Growth factors play an
important role in healing wounds and in embryonic development.
Diseases Associated with the Cell Cycle Mechanism

The cell cycle control mechanism is perfectly timed. Cell growth is regulated very carefully because the
consequences of an unregulated cell growth are very severe. A diminishing loss of control in the cell cycle leads to
the proliferation of cancer. There is loss of integrity in the cell processes and cells may even “forget” to die. Cancer
cells are basically cells that just keep on dividing.
When cancer cells invade nearby normal tissues, or spread through the walls of lymph vessels or blood
vessels, they begin to infect other healthy cells. The process by which cancer cells spread from where they
originated is called metastasis. Cancer cells that have begun to metastasize invade other healthy cells, even tissues,
eventually shutting down organs and systems, and inflicting damage that is enough to kill its host.

General Concepts of Cell Division

Cell Division—involves the distribution of identical genetic material or DNA to two daughter cells.
What is most remarkable is the fidelity with which the DNA is passed along, without dilution or error, from one
generation to the next. Cell Division functions in reproduction, growth, and repair.
Core Concepts:
• All organisms consist of cells and arise from preexisting cells.
• Mitosis is the process by which new cells are generated.
• Meiosis is the process by which gametes are generated for reproduction.
• The Cell Cycle represents all phases in the life of a cell.
• DNA replication (S phase) must precede mitosis so that all daughter cells receive the same complement of
chromosomes as the parent cell.
• The gap phases separate mitosis from S phase. This is the time when molecular signals mediate the switch
in cellular activity.
• Mitosis involves the separation of copied chromosomes into separate cells.
• Unregulated cell division can lead to cancer.
• Cell cycle checkpoints normally ensure that DNA replication and mitosis occur only when conditions are
favorable and the process is working correctly.
• Mutations in genes that encode cell cycle proteins can lead to unregulated growth, resulting in tumor
formation and ultimately invasion of cancerous cells to other organs.
The Cell Cycle control system is driven by a built-in clock that can be adjusted by external stimuli (i.e., chemical
messages).

Checkpoint—a critical control point in the Cell Cycle where ‘stop’ and ‘go-ahead’ signals can regulate the cell cycle.
• Animal cells have built-in ‘stop’ signals that halt the cell cycles and checkpoints until overridden by
‘go-ahead’ signals.
• Three major checkpoints are found in the G1, G2, and M phases of the Cell Cycle.
The G1 Checkpoint—the Restriction Point
• The G1 checkpoint ensures that the cell is large enough to divide and that enough nutrients are
available to support the resulting daughter cells.
• If a cell receives a ‘go-ahead’ signal at the G1 checkpoint, it will usually continue with the Cell
Cycle.
• If the cell does not receive the ‘go-ahead’ signal, it will exit the Cell Cycle and switch to a non-dividing
state called G0.
• Most cells in the human body are in the G0 phase.
The G2 Checkpoint—ensures that DNA replication in S phase has been successfully completed.
The Metaphase Checkpoint—ensures that all of the chromosomes are attached to the mitotic spindle by a
kinetochore.

Kinase - a protein which activates or deactivates another protein by phosphorylating them. Kinases give the ‘go-
ahead’ signals at the G1 and G2 checkpoints. The kinases that drive these checkpoints must themselves be
activated.
• The activating molecule is a cyclin, a protein that derives its name from its cyclically fluctuating
concentration in the cell. Because of this requirement, these kinases are called cyclin-dependent
kinases or CDKs.
• Cyclins accumulate during the G1, S, and G2 phases of the Cell Cycle.
• By the G2 checkpoint, enough cyclin is available to form MPF complexes (aggregations of CDK and
cyclin) which initiate mitosis.
• MPF functions by phosphorylating key proteins in the mitotic sequence.
• Later in mitosis, MPF switches itself off by initiating a process which leads to the destruction of cyclin.
• CDK, the non-cyclin part of MPF, persists in the cell as an inactive form until it associates with new
cyclin molecules synthesized during the interphase of the next round of the Cell Cycle.
 Stages of Mitosis

Mitosis (apparent division)—is nuclear division; the process by which the nucleus divides to produce two new
nuclei. Mitosis results in two daughter cells that are genetically identical to each other and to the parental cell from
which they came.
Cytokinesis—is the division of the cytoplasm. Both mitosis and cytokinesis last for around one to two hours.

Prophase—is the preparatory stage, during prophase, centrioles move toward opposite sides of the nucleus.
The initially indistinct chromosomes begin to condense into visible threads.
• Chromosomes first become visible during early prophase as long, thin, and intertwined filaments but by
late prophase, chromosomes are more compacted and can be clearly discerned as much shorter and
rod-like structures.
• As the chromosomes become more distinct, the nucleoli also become more distinct. By the end of
prophase, the nucleoli become less distinct, often disappearing altogether.
Metaphase—is when chromosomes become arranged so that their centromeres become aligned in one place,
halfway between the two spindle poles. The long axes of the chromosomes are 90 degrees to the spindle axis. The
plane of alignment is called the metaphase plate.
Anaphase—is initiated by the separation of sister chromatids at their junction point at the centromere.
The daughter chromosomes then move toward the poles.
Telophase—is when daughter chromosomes complete their migration to the poles. The two sets of progeny
chromosomes are assembled into two-groups at opposite ends of the cell. The chromosomes uncoil and assume
their extended form during interphase. A nuclear membrane then forms around each chromosome group and the
spindle microtubules disappear. Soon, the nucleolus reforms.