UNIT 4: Cell Cycle Checkpoints

and Stages
Prepared by:
MELODY T. TAMONTE, LPT, MAEd
The cell cycle is a fairly complicated process. Like in rapidly dividing human
cells with a 24-hour cell cycle, the G1 phase lasts approximately nine
hours, the S phase lasts 10 hours, the G2 phase lasts about four and one-
half hours, and the M phase lasts approximately one-half hour. In early
embryos of fruit flies, the cell cycle is completed in about eight minutes. The
timing of events in the cell cycle is controlled by mechanisms that are both
internal.
The Cell Cycle Phases
Did you know that when we add all the
chromosomes up, each cell actually
contains about 2m of DNA and this DNA
has to fit into a tiny nucleus of 5-10ưm in
diameter. This is like trying to stuff a piece
of string 2km long.
Chromosomes, Chromatin, Chromatid: Which
is which!

Chromatin is an uncoiled mass of genetic material composed of DNA

and proteins that condense to form chromosomes. It is composed of
small proteins called Histones which help in the coiling of Chromatin
so that this very long thread like structure will become a compacted
chromosomes.
 Chromosomes are single-stranded groupings of coiled chromatin.
Chromatin must exist in chromosomes or coiled form to prevent it from
being entangled during cell division which ensures that all the information
from the DNA are properly copied and not entangled.
Chromatid is either of the two strands of a replicated
chromosome. Chromatids connected by a centromere are
called sister chromatids and has the familiar X shape.

NOTE: See for yourself how DNA transforms from

chromatin, chromosomes and chromatid through the help
of histone proteins by visiting the link below (if internet is
available).
https://youtu.be/gbSIBhFwQ4s
Centromere is the point of attachment of between sister chromatid.
Within the chromatid, a kinetochore can be found.
Kinetochore is the structure where the spindle fiber attaches during
cell division.
Do you know where the spindle fiber that attaches to
the kinetochore within the centromere come from?

The spindle is necessary to equally divide the

chromosomes in two daughter cells during mitosis and
meiosis. This spindle fibers are protein fibers called
microtubules which extend from a pair of centrioles.
Moreover, these centrioles are produced by centrosome
which is the microtubule organizing center of the cell.
Cell cycle is the series of events that occur in a cell to prepare cell
division and to produce two new daughter cells.
Phases of cell cycle include two major activities:
1. Interphase (G1, S,G2)
2. M-phase (Mitotic phase)

Interphase is the longest phase of the cell cycle process. It is also the
known as the resting phase. Although the cell is at rest but it is
metabolically active. The metabolic activities of the cell can be
observed through cell growth, production of nutrients and enzymes
and replication of DNA.
 1. Interphase has 3 sub-stages:
1. G1 phase (Gap1 phase/Growth 1 phase)
2. S-phase (Synthesis phase)
3. G2 phase (Gap2 phase/Growth 2 phase)

G1 phase (Gap1 phase/Growth 1 phase) the cell increases in size, protein synthesis also
occurs enable the cell to increase the amount of cytosol.
Synthesis phase is the longest and the most essential stage of interphase. It is due to the
complexity of the replication of genetic material which results to the duplication of DNA
prior to the cell division process.
G2 phase (Gap2 phase/Growth 2 phase) is the final stage where the cell prepares itself for
cell division process, and also ensures that the DNA replication completes.
 
Cell cycle checkpoints verify whether all the cellular
activities are accurately completed at each stage of
interphase.
In eukaryotic cells, there are three major checkpoints that
control the cell cycle process. They are:
1. G1 checkpoint at the G1/S transition
2. G2 checkpoint at the G2/M transition
3. Spindle checkpoint, transition from metaphase and
anaphase
2. M ( Mitotic Phase)
In this phase, the cell will undergo prophase, metaphase, anaphase and telophase.
G1 checkpoint checks the following:

a. Cell’s size (Does the cell increase its size or large enough for cell
division?)
b. Nutrients (Does the cell have enough reserve energy and nutrients
for cell division?)
c. DNA integrity (Is any part of the DNA damaged?)
d. Molecular signals (Does the cell receives growth factors and other
signals from neighboring cell?)
 
 If the cell does not comply with the following factors, cell cycle will
stop and enters the G0 phase called the resting state. Some cell
stays in G0 phase permanently, while others proceed to divide if the
condition of the cell improves.
G2 checkpoint/ DNA Synthesis Checkpoint checks the following:
- in which the checking occurs during the S phase, in which the
cell’s DNA is being checked for correct replication down to the last
nucleotide. If so, the cell will proceed to the mitosis.
a. DNA integrity (Is any part of the DNA damaged?)
b. DNA replication (Is the DNA replication completed in the S phase?)
If there is an error, the cell will pause at the G2 phase and allow for
some repairs. If the damage is within the DNA, the cell cycle will
pause and let the cell complete the DNA replication or repair it. But if
the damage cell is irreparable, the cell will undergo apoptosis or cell
death. It is the self-destruction mechanism of the cell to ensure that
the damaged DNA is not passed on the daughter cells and also
important in preventing cancer. There are some cells that never or
rarely divide like matured cardiac muscle and nerve cell that
permanently retains in G0.
Mitosis Checkpoint /Metaphase checkpoint or Spindle
checkpoint
- occurs at metaphase stage of mitosis. It is regulated by Anaphase-
Promoting Complex (APC). It checks whether all chromosomes are
properly attached to the spindle fibers and its alignment at the
metaphase plate. If there are mistakes, the cell delays it anaphase
process.
- is the final checkpoint before division. The checking occurs during mitosis
to make sure that the cell has already completed the mitotic process. If the
requirement is fulfilled, the cell divides and the cell cycle repeats.
Cancer is the result of the unregulated process of the cell cycle due to the
breakdown of the mechanisms that controls the entire process. It happens
during the synthesis phase, wherein the cell cannot determine the changes in
the DNA sequence that code for the specific regulatory molecules.
Oncogenes are the genes that cause the cell to become cancerous.
Proto-oncogenes are the genes that code for positive regulators
during cell cycle. When these normal genes are altered by mutation it
can be an oncogenes leading to cancer cells formation.
Tumor suppressor genes are healthy normal genes that slow down
cell division, helps to repair DNA mistakes and also cell apoptosis or
cell death. It codes for the negative regulator protein, when activated
can prevent the cell from uncontrolled division. But when tumor
suppressor gene does not work properly, cell division will be out of
control and it can also lead to cancer.
 THE CELL CYCLE REGULATORS

Cell cycle regulators are proteins that function to detect and repair DNA damage and prevent
rapid uncontrolled cell division. The regulations are dependent also on signaling relay of
the cell.

THE REGULATORY MOLECULES

Cyclins are regulatory subunits that do not have a catalytic function. The cell synthesizes this
during the cell cycle. The cycline-dependent kinases (CDK), is a catalytic subunit that
becomes active only when cyclin is bound to it. The binding of CDKs and cyclins function
together to phosphorylate and stimulate or deactivate target molecule in the succeeding
steps of the cell cycle. Specific types of cyclin and CDK kinases and cyclin combination
determine specific target molecule (protein).
 What I Have Learned ?

1. Cell cycle is the series of events that occur in a cell to prepare cell division and
to produce two new daughter cells.
2. Cell cycle checkpoints verify whether all the cellular activities are accurately
completed at each stage of interphase.
3. Interphase is the longest phase of the cell cycle process. It is also known as the
resting phase.
4. G0 phase called the resting state.
5. G1 phase (Gap1 phase) the cell increases in size, protein synthesis also occurs
enable the cell to increase the amount of cytosol.
6. Synthesis phase is the longest and the most essential stage of interphase.
It is due to the complexity of the replication of genetic material which results
to the duplication of DNA prior to the cell division process.
7. G2 phase (Gap2 phase) is the final stage where the cell prepares itself for
cell division process, and also ensures that the DNA replication completes.
8. G1 checkpoint checks the cell size, nutrients, DNA and molecular
signals.
9. G2 checkpoint checks the DNA and complete DNA replication in S phase.
10. Metaphase checkpoint or Spindle checkpoint occurs at metaphase stage
of mitosis and regulated by Anaphase-promoting complex (APC).
11. Cancer is the result of the unregulated process of the cell cycle due to the
breakdown of the mechanisms that controls the entire process. It happens during
the synthesis phase, wherein the cell cannot determine the changes in the DNA
sequence that code for the specific regulatory molecules.
12. Oncogenes are the genes that cause the cell to become cancerous.
13. Proto-oncogenes are the genes that code for positive regulators during cell cycle.
When these normal genes are altered by mutation it can be an oncogenes leading to
cancer cells formation.
14. Tumor suppressor genes are healthy normal genes that slow down cell division,
helps to repair DNA mistakes and also cell apoptosis or cell death. It codes for the
negative regulator protein, when activated can prevent the cell from uncontrolled
division. But when tumor suppressor gene does not work properly, cell division will
be out of control and it can also lead to cancer.
“The fundamental biological
variant is DNA”.

~ Jacques Monod ~