Cell Cycle Regulation

In this lesson, you will be given a chance to review the basic principles in the cell cycle and then learn its regulatory
processes. The focus will be on the topics about the general overview of the cell cycle control system and the
checkpoints. The last part will be all about the molecular components that drive these dynamic processes.

Jayzon G. Bitacura, MSc., RMicro

Assistant Professor III
Department of Biological Sciences
College of Arts and Sciences
Visayas State University
 Learning Outcomes
At the end of this lesson, you will be able to:
1. review the general process of the cell cycle.
2. differentiate the major regulatory transitions of the cell
cycle control system.
3. identify the cell cycle control checkpoints; and
4. identify the components of the cell cycle control system

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Motivation
Match the following stages of the cell cycle to the figures below: Interphase, Prophase, Metaphase,
Anaphase, Telophase.

You are correct! The figure in number 1 is at Metaphase, 2 is Telophase, 3

is Anaphase, 4 is Interphase, and 5 is Prophase.

How does the cell regulate these phases so that

they could produce cells that are identical to
themselves?
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 Review of Eukaryotic Cell Cycle
A typical eukaryotic cell represented by a human cell in culture divides approximately every 24 hours.
Two basic parts comprise the cell cycle. These are the mitosis and interphase. Mitosis, or nuclear
division, is the most dramatic stage of the cell cycle. It is the time when the separation of daughter
chromosomes occur and usually ends with cell division or cytokinesis.

Mitosis and cytokinesis last for approximately an hour, so

about 95% of the cell cycle is spent in interphase, the
period between mitoses.
Cell-shape-mitosis.png" by UraniumMonkey

At interphase, the chromosomes are decondensed and

distributed throughout the nucleus, so the nucleus appears
morphologically uniform. However, at the molecular level,
is licensed with CC BY-SA 4.0

interphase is the time during which both DNA replication

and cell growth occur as the cell prepares to divide.

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 Review of Eukaryotic Cell Cycle
The cell maintains its growth rate throughout the interphase. Most of the dividing cells double in size
between one mitosis to the next. Conversely, DNA is synthesized during only a portion of the interphase.
DNA synthesis divides the cycle of eukaryotic cells into four discrete phases.
These phases are the M phase, G1 phase (gap 1), S phase, and G2 phase (gap 2).
What are the distinct processes that occur within these phases?

The M phase of the cell cycle is the period when mitosis

Cell-shape-mitosis.png" by UraniumMonkey

occurs. This is usually followed by cytokinesis. The mitotic

phase is further divided into 4 major phases that include
Prophase, Metaphase, Anaphase, and Telophase.
is licensed with CC BY-SA 4.0

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 Review of Eukaryotic Cell Cycle

Cell-shape-mitosis.png" by UraniumMonkey is licensed with CC BY-SA

G1 phase is the one that follows the M phase, which
corresponds to the interval (gap) between mitosis and
initiation of DNA replication.

S phase is the synthesis phase following G1. During this

phase, DNA replication takes place.

G2 phase follows the completion of DNA synthesis. During

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this phase, the proteins are synthesized in preparation for

mitosis.

So how are these processes regulated?

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Regulation of the Cell Cycle

Extracellular signals from the environment regulate the progression of cells through the division cycle.
Moreover, internal signals monitor and coordinate the various processes that take place during different
cell cycle phases.

An example of cell cycle regulation by extracellular signals is provided by the effect of growth factors on
animal cell proliferation.

Also, various cellular processes that occur in cells, such as

growth, DNA replication, and mitosis, must be coordinated
during the progression of the cell cycle.

This is accomplished by a series of control points that

regulate progression through various phases of the cell
cycle (Alberts et al., 2015).

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Cell Cycle Control System
In eukaryotic cells, the cell-cycle control system generally governs cell-cycle progression at three major
regulatory transitions. What are these regulatory transitions?

Start (or the restriction point) in late G1. It is where

the cell commits to cell-cycle entry and
chromosome duplication. Passage through Start is
controlled by external signals such as the availability
of nutrients, as well as by cell size.
Open Stax. Located at:
http://cnx.org/contents/185cbf
87-c72e-48f5-b51e-f14f21b5e
G2/M transition. It is where the control system checks if all abd@9.17:1/Biology.
DNA has been replicated already and if the environment is License: CC BY: Attribution

favorable for nuclear division and triggers the early mitotic

events that lead to chromosome alignment on the mitotic
spindle in metaphase. The system checks if all DNA has
been replicated already and if the environment is favorable
to proceed to the next phase of the cycle.

Metaphase-to-anaphase transition, where the control

system checks if all chromosomes are already attached
to the spindle and stimulate sister-chromatid separation,
leading to the completion of mitosis and cytokinesis.
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Cell Cycle Control System
If problems are detected inside or outside of the cell, the control system blocks progression through each
of the transitions. If the control system senses problems in the completion of DNA replication, for
example, it will hold the cell at the G2/M transition until those problems are solved.

Similarly, if extracellular conditions are not

appropriate for cell proliferation, the control
system blocks progression through Start,
thereby preventing cell division until
conditions become favorable.

Open Stax. Located at:

http://cnx.org/contents/185cbf87-c72e-48f5-b51e-f14f21b5eabd@9.17:1/Biology.
License: CC BY: Attribution 9
Cell Control Checkpoints
Coordination with one another of the events that take place during different stages of the cell cycle is
important so that they occur in the appropriate sequence. In most cells, the coordination between
different phases of the cell cycle is dependent on a series of cell cycle checkpoints that prevent entry
into the next phase of the cell cycle until the events of the preceding phase have been completed. Two
important checkpoints in eukaryotic cells ensure that complete genomes are transmitted to daughter
cells. These are the DNA damage checkpoints and the spindle assembly checkpoint (Cooper, 2019).

How do they differ?

DNA damage checkpoints function to ensure that damaged

DNA is not replicated and passed on to daughter cells. These
checkpoints sense damaged or incompletely replicated DNA
and coordinate further cell cycle progression with the
completion of DNA replication or repair. DNA damage
checkpoints function in G1, S, and G2 and lead to cell cycle
arrest in response to damaged or unreplicated DNA.

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Cell Control Checkpoints
Coordination with one another of the events that take place during different stages of the cell cycle is
important so that they occur in the appropriate sequence. In most cells, the coordination between
different phases of the cell cycle is dependent on a series of cell cycle checkpoints that prevent entry
into the next phase of the cell cycle until the events of the preceding phase have been completed. Two
important checkpoints in eukaryotic cells ensure that complete genomes are transmitted to daughter
cells. These are the DNA damage checkpoints and the spindle assembly checkpoint (Cooper, 2019).

How do they differ?

Spindle assembly checkpoint maintains the integrity of the genome occurring towards the end of
mitosis. This checkpoint sees to it that the alignment of chromosomes on the mitotic spindle is
successful. This is important to ensure that a complete set of chromosomes is distributed accurately to
the daughter cells.
Otherwise, failure of one or more chromosomes to align properly
on the spindle causes mitosis to arrest at metaphase, prior to the
segregation of the newly replicated chromosomes to daughter
nuclei.

As a result of the spindle assembly checkpoint, the chromosomes

do not separate until a complete complement of chromosomes
has been organized for distribution to each daughter cell. 11
Components of the Cell Cycle Control
System
● The two key components of the cell-cycle control system are the cyclin and the
cyclin-dependent kinases (Cdks).
● When cyclin forms a complex with Cdk, the protein kinase is activated to trigger specific
events. Without cyclin, Cdk is inactive.
● Cyclins are of four classes.
○ Each class is defined by the stage of the cell at which they bind Cdks and function
(Alberts et al., 2015).
○ All eukaryotic cells require three of these classes:
■ G1/S cyclins
■ S-cyclins
■ M-cyclins
■ G1-cyclins

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1. G1/S-cyclins activate Cdks in late G1
and thereby trigger progression through
Start, resulting in the commitment to
cell-cycle entry. Their levels fall in the S
phase.
2. S-cyclins are those that bind Cdks soon
after progression through Start and help
stimulate chromosome duplication. The
levels of S-cyclin remain elevated until
mitosis. These cyclins also contribute to
the control of some early mitotic events.
3. M-cyclins are those that activate Cdks
that stimulate entry into mitosis at the
G2/M transition. Their levels fall in
mid-mitosis.
4. In most cells, the fourth class of cyclins
called the G1-cyclins helps govern the
activities of the G1/S-cyclins, which
control progression through Start in late
G1.
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Components of the Cell Cycle Control
System
● As observed in yeast cells, a single Cdk protein binds all classes of cyclins and triggers
different cell-cycle events by changing cyclin partners at different stages of the cycle.
● Conversely, in vertebrate cells, there are four Cdks.
● Two interact with G1-cyclins, one with G1/S- and S-cyclins, and one with S- and M-cyclins.
● In this lesson, we could simply refer to the different cyclin-Cdk complexes as G 1-Cdk, G1/S-Cdk,
S-Cdk, and M-Cdk.

How do the different cyclin-Cdk complexes trigger different cell-cycle events?

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Some reports stated that

● The cyclin protein does not simply activate its Cdk

partner but also directs it to specific target proteins.
● As a result, each cyclin-Cdk complex
phosphorylates a different set of substrate proteins.
● The same cyclin-Cdk complex can also induce
different effects at different times in the cycle,
probably because of the accessibility of some Cdk
substrates that changes during the cell cycle.
● Certain proteins that function in mitosis, for
example, may become available for phosphorylation
in G2.

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 Summary Questions

● What are the general processes involved

in the cell cycle?
● What are the major regulatory
transitions of the cell cycle, and how do
they differ?
● What are the different cell cycle control
checkpoints, and how do they function?
● What are the components of the cell
cycle control system?

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Acknowledgment: Mr. Ern Oliver C. Balondo for
the help in making the slide presentation.

Contact information:
jayzon.bitacura@vsu.edu.ph
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