12

General Biology 1
Quarter 1 – Module 5:
Cell Cycle (with M Phase)
Development Team of the Module
Writers: Ma. Angelica D. Guban
Editors: : Evelyn D. Dulino, Ph.D.
Reviewer: Ryan Cutamora
Illustrator:
Layout Artist:
Management Team: Dr. Carlito D. Rocafort
Dr. Job S. Zape Jr.
Eugene Adrao
Elaine Balaogan
Elpidia B. Bergado Ed.D, CID Chief
Noel S. Ortega, Division EPS-LRMS
Dr. Josephine Monzaga
Lesson
Cell Cycle Checkpoints and
1 Stages

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 and external to the cell.

In order to make sure everything goes right, there are checkpoints in the cycle. Let’s
learn about these and how they help control the cell cycle but first familiarize
yourself with the important terms below:

Histones for the Win

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 5-10 ưm in
diameter. This is like trying to stuff a piece of string 2km long. To do this seemingly
impossible task, cells devised an ingenious packaging system: it wraps DNA around
Histone proteins.

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 CHECKPOINTS

Checkpoint Consideration #1:

Regulation of the Cell Cycle by External Events

Both the initiation and inhibition of cell division are triggered by events
external to the cell when it is about to begin the replication process. An event may
be as simple as the death of a nearby cell or as sweeping as the release of growth-
promoting hormones, such as human growth hormone (HGH). A lack of HGH can
inhibit cell division, resulting in dwarfism, whereas too much HGH can result in
gigantism. Crowding of cells can also inhibit cell division. Another factor that can
initiate cell division is the size of the cell; as a cell grows, it becomes inefficient due
to its decreasing surface-to-volume ratio. The solution to this problem is to divide.
Whatever the source of the message, the cell receives the signal, and a series
of events within the cell allows it to proceed into interphase. Moving forward from
this initiation point, every parameter required during each cell cycle phase must be
met or the cycle cannot progress.
 Checkpoint Consideration #2:
Regulation at Internal Checkpoints

It is essential that the daughter cells produced 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 an
abnormal cell. To prevent a compromised cell from continuing to divide, there are
internal control mechanisms that operate at three main cell cycle checkpoints. A
checkpoint is one of several points in the eukaryotic cell cycle at which the
progression of a cell to the next stage in the cycle can be halted until conditions are
favorable. These checkpoints occur near the end of G1, at the G2/M transition, and
during metaphase (Figure 1).

Figure 1. The cell cycle is controlled at three checkpoints.

The 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. This checkpoint checks the following:
 Adequate reserves of protein and cell size
 There is a check for genomic DNA damage
Note: A cell that does not meet all the requirements will not be allowed to progress
into the S phase. The cell can halt the cycle and attempt to remedy the problematic
condition, or the cell can advance into G 0 and await further signals when conditions
improve.

The G2 Checkpoint
The G2 checkpoint bars entry into the mitotic phase if certain conditions are not
met. As at the G1 checkpoint, it checks the following:
 Assessment of cell size and protein reserves
 Ensure that all of the chromosomes have been replicated
 Make sure that the replicated DNA is not damaged.
NOTE: If the checkpoint mechanisms detect problems with the DNA, the cell cycle is
halted, and the cell attempts to either complete DNA replication or repair the
damaged DNA.
 The M Checkpoint
The M checkpoint occurs near the end of the metaphase stage of
Karyokinesis. The M checkpoint checks the following:
 Determines whether all the sister chromatids are correctly attached to the spindle
microtubules.
NOTE: 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 at least two spindle fibers arising from
opposite poles of the cell.

Regulator Molecules of the Cell Cycle

In addition to the internally controlled checkpoints, there are two groups of
intracellular molecules that regulate the cell cycle. These regulatory molecules
either promote progress of the cell to the next phase (positive regulation) or halt
the cycle (negative regulation). Regulator molecules may act individually, or they
can influence the activity or production of other regulatory proteins. Therefore, the
failure of a single regulator may have almost no effect on the cell cycle, especially if
more than one mechanism controls the same event. Conversely, the effect of a
deficient or non-functioning regulator can be wide-ranging and possibly fatal to the
cell if multiple processes are affected.

Positive Regulation of the Cell Cycle

Two groups of proteins, called cyclins and Cyclin-dependent kinases (CDk), are
responsible for the progress of the cell through the various checkpoints. The levels
of the four Cyclin proteins fluctuate throughout the cell cycle in a predictable
pattern (Figure 2). Increases in the concentration of Cyclin proteins are triggered by
both external and internal signals. After the cell moves to the next stage of the cell
cycle, the cyclins that were active in the previous stage are degraded.

In Figure 2. The concentrations of cyclin proteins change throughout the cell

cycle. There is a direct correlation between Cyclin accumulation and the three major
cell cycle checkpoints. Also note the sharp decline of cyclin levels following each
checkpoint (the transition between phases of the cell cycle), as Cyclin is degraded by
cytoplasmic enzymes.
Cyclins regulate the cell cycle only when they are tightly bound to CDk. To be
fully active, the CDk/cyclin complex must also be phosphorylated in specific
locations.

Like all kinases, Cdks are enzymes (kinases) that phosphorylate other
proteins. Phosphorylation activates the protein by changing its shape. The proteins
phosphorylated by Cdks are involved in advancing the cell to the next phase
(Figure 3). The levels of CDk proteins are relatively stable throughout the cell cycle;
however, the concentrations of cyclin fluctuate and determine when CDk/cyclin
complexes form. The different cyclins and Cdks bind at specific points in the cell
cycle and thus regulate different checkpoints.

Cyclin-dependent kinases (Cdks) are protein kinases that, when fully

activated, can phosphorylate and thus activate other proteins that advance the cell
cycle past a checkpoint. To become fully activated, a CDk must bind to a cyclin
protein and then be phosphorylated by another kinase.

Since the cyclic fluctuations of cyclin levels are based on the timing of the
cell cycle and not on specific events, regulation of the cell cycle usually occurs by
either the CDk molecules alone or the CDk/cyclin complexes. Without a specific
concentration of fully activated cyclin/CDk complexes, the cell cycle cannot proceed
through the checkpoints. Please take time to analyze the diagram below!

Although the cyclins are the main regulatory molecules that determine the
forward momentum of the cell cycle, there are several other mechanisms that fine-
tune the progress of the cycle with negative, rather than positive, effects. These
mechanisms essentially block the progression of the cell cycle until problematic
conditions are resolved. Molecules that prevent the full activation of Cdks are called
CDk inhibitors. Many of these inhibitor molecules directly or indirectly monitor a
particular cell cycle event. The block placed on Cdks by inhibitor molecules will not
be removed until the specific event that the inhibitor monitors is completed.

Negative Regulation of the Cell Cycle

 The second group of cell cycle regulatory molecules are negative regulators.
Negative regulators halt the cell cycle. Remember that in positive regulation, active
molecules cause the cycle to progress.

The best understood negative regulatory molecules are retinoblastoma

protein (Rb), p53, and p21. Retinoblastoma proteins are a group of tumor-
suppressor proteins common in many cells. Much of what is known about cell cycle
regulation comes from research conducted with cells that have lost regulatory
control. All three of these regulatory proteins were discovered to be damaged or non-
functional in cells that had begun to replicate uncontrollably (became cancerous). In
each case, the main cause of the unchecked progress through the cell cycle was a
faulty copy of the regulatory protein.

Rb, p53, and p21 act primarily at the G1 checkpoint. P53 is a multi-
functional protein that has a major impact on the commitment of a cell to division
because it acts when there is damaged DNA in cells that are undergoing the
preparatory processes during G1. If damaged DNA is detected, p53 halts the cell
cycle and recruits enzymes to repair the DNA. If the DNA cannot be repaired, p53
can trigger apoptosis, or cell suicide, to prevent the duplication of damaged
chromosomes. As p53 levels rise, the production of p21 is triggered. P21 enforces
the halt in the cycle dictated by p53 by binding to and inhibiting the activity of the
CDk/cyclin complexes. As a cell is exposed to more stress, higher levels of p53 and
p21 accumulate, making it less likely that the cell will move into the S phase.

Cancer is the result of unchecked cell division caused by a breakdown of the

mechanisms that regulate the cell cycle. The loss of control begins with a change in
the DNA sequence of a gene that codes for one of the regulatory molecules. Faulty
instructions lead to a protein that does not function as it should. Any disruption of
the monitoring system can allow other mistakes to be passed on to the daughter
cells. Each successive cell division will give rise to daughter cells with even more
accumulated damage. Eventually, all checkpoints become nonfunctional, and
rapidly reproducing cells crowd out normal cells, resulting in a tumor or leukemia
(blood cancer).

Stages of Mitosis
 Meiosis Time!
Meiosis
The process that produces haploid gametes is meiosis. Meiosis is a type of cell division in which
the number of chromosomes is reduced by half. It occurs only in reproductive cells of the
organisms. During meiosis, homologous chromosomes separate, and the haploid cells that form
have only one chromosome from each pair. Two cell divisions occur during meiosis, and a total
of four haploid cells are produced. The two cell divisions are called meiosis I and meiosis II.

Phases of Meiosis

Meiosis I begins after DNA replicates during interphase. In both meiosis I and meiosis II, cells go
through the same four phases as mitosis. However, there are important differences between
meiosis I and mitosis.

Meiosis I

1. Prophase I: The nuclear envelope begins to break down, and the chromosomes condense.
Centrioles start moving to opposite poles of the cell, and a spindle begins to form. Importantly,
homologous chromosomes pair up, which is unique to prophase I. In here crossing over
happens where the homologous chromosomes pair up with each other and exchange different
segments of genetic material to form recombinant chromosomes. In simple words genetic trait
both from your mother and father are recombining and exchanging traits accordingly which
gives way to the mixing and matching of traits. It is also the reason why there is uniqueness
among organisms and even among siblings.

2. Metaphase I: Spindle fibers attach to the paired homologous chromosomes. The paired
chromosomes line up along the equator of the cell. This occurs only in metaphase I. In
metaphase of mitosis and meiosis II, it is sister chromatids that line up along the equator of
the cell.

3. Anaphase I: Spindle fibers shorten, and the chromosomes of each homologous pair start to
separate from each other. One chromosome of each pair moves toward one pole of the cell,
and the other chromosome moves toward the opposite pole.
4. Telophase I and Cytokinesis: The spindle breaks down, and new nuclear membranes form.
The cytoplasm of the cell divides, and two haploid daughter cells result. The daughter cells
each have a random assortment of chromosomes, with one from each homologous pair. Both
daughter cells go on to meiosis II.

Meiosis II

1. Prophase II: The nuclear envelope breaks down and the spindle begins to form in
each haploid daughter cell from meiosis I. The centrioles also start to separate.

2. Metaphase II: Spindle fibers line up the sister chromatids of each chromosome along
the equator of the cell.

3. Anaphase II: Sister Chromatids separate and move to opposite poles.

4. Telophase II and Cytokinesis : The spindle breaks down, and new nuclear membranes
form. The cytoplasm of each cell divides, and four haploid cells result. Each cell has a
unique combination of chromosomes.

SIGNIFICANCE OF MITOSIS AND MEIOSIS

Real Life Connect!!

o Mitosis plays a significant role in the development of embryos as well as for

the growth of our bodies.
o When we are wounded or when our body needs healing, new cells are created
to replace those that were damaged through mitosis.
o To replace lost arms starfish use mitosis.
o Hydra use mitosis to produce genetically identical offspring.
o Meiosis plays a significant role in preparing the cells needed for sexual
reproduction. Without it, life will not perpetuate.
o Meiosis ensures that all organisms contain the correct number of
chromosomes which lessen the probability of birth defects or disorders.

Values Connect!!

o No two people are exactly alike because of crossing over so RESPECT

each other’s differences.

o You are wonderfully mad, you are unique!

What’s More
 Challenge # 1: CELL CYCLE CHECKPOINTS

EXPRESS IN WRITING
Use your own words to answer the questions below:
A. Why are cell cycle checkpoints important?
B. Describe how cancer cell is produced.
C. Describe the functions of the following in cell division:
A. nucleus
B. DNA
C. centromeres
D. Histone protein
E. Spindle fibers
F. Cyclins

Challenge # 2: CELL CYCLE CHECKPOINTS

Direction: Complete the table below using what you have learned from the concepts
presented above.
Checkpoint Factors needed to Needed materials/ Duration CDK
proceed with the molecules (Present or
cell cycle Absent)
1.

2.

3.

4.

Challenge #3: MITOSIS

Illustration Time!
 Enhance your creativity and critical thinking skills by making your own illustration
of the phases of mitosis, make sure to write appropriate descriptions for each
phase.. Given 2n=6.

Prophase Metaphase

Anaphase Telophase

Challenge #4: MEIOSIS

EXPRESS IN WRITING!
Direction: Answer briefly and concisely

1. Define Meiosis.

2. Is the DNA replicated after meiosis I? Why or why not?

3. Describe the main difference between metaphase I and metaphase II.

4. State the phase where each of the following processes occurs:

(a) Sister chromatids separate,
(b) Homologous chromosomes form pairs
(c) Two haploid cells form.

5. What is final product of meiosis?

 Challenge #5: MEIOSIS
Illustration Time!
Enhance your creativity and critical thinking skills by making your own illustration
of the phases of meiosis using the descriptions presented above, make sure to write
appropriate descriptions or labels for each phase. Given 2n=6. See to it to use two
different colors of pen to easily distinguish the maternal and paternal traits during crossing over.

Prophase 1 Metaphase 1

Anaphase 1 Telophase 1

Prophase 2 Metaphase 2

Anaphase 2 Telophase 2

What I Have Learned

 1. Each step of the cell cycle is monitored by internal controls called
checkpoints. There are three major checkpoints in the cell cycle: one near the end of
G1, a second at the G2/M transition, and the third during metaphase. Positive
regulator molecules allow the cell cycle to advance to the next stage. Negative
regulator molecules monitor cellular conditions and can halt the cycle until specific
requirements are met.
2. For the cell to move past each of the checkpoints, all positive regulators
must be “turned on,” and all negative regulators must be “turned off.”
3. Mitosis is a process of cell division that results in two genetically identical
daughter cells developing from a single parent cell. Its phases beginning interphase
are PROPHASE, METAPHASE, ANAPHASE and TELOPHASE.
4. Meiosis is the division of a germ cell involving two fissions of the nucleus
and giving rise to four gametes or sex cells, each possessing half the number of
chromosomes of the original cell. Its phases beginning interphase are PROPHASE 1,
METAPHASE 1, ANAPHASE 1, TELOPHASE 1, PROPHASE 2, METAPHASE 2,
ANAPHASE 2, and TELOPHASE 2.

What I Can Do

MITOSIS AND MEIOSIS COMPARISON TABLE

Basis of Comparison Mitosis Meiosis

1. Type of Cell where the

process occurs

2. Number of cell divisions

3. Number of
chromosomes in parent
cell and daughter cell

4. Needed Checkpoints

5. Stages/ Phases

6. Final product

7. Example

3 Points Exit
 Three concepts I learned:
1. ________________________________________________
2. ________________________________________________
3. ________________________________________________
Two real-life realizations after finishing the topic
1. _________________________________________________
2. _________________________________________________
One most favorite part of the lesson
1. _________________________________________________

Multiple Choice. Choose the letter of the best answer. Write the chosen letter on a separate
sheet of paper.
1. Which of the following is the main reason why DNA must exist in chromosome form?
a. To favor the formation of sister chromatids
b. To allow the protein histones to carry out its task
c. To avoid the genetic material to be tangled away during cell division
d. To promote the formation of spindle fibers

2. Which phase of mitosis is shown in the picture?

a. Prophase c. Anaphase
b. Metaphase d. Telophase

3. If there are 20 chromosomes in a cell at metaphase, how many chromosomes are there is each
daughter cell following cytokinesis of mitosis?
a. 10 b. 20 c. 40 d. 80

4. The reconstruction of the nuclear membrane takes place in what phase of the cell cycle?
a. Prophase c. Anaphase
b. Metaphase d. Telophase

5. Which of the following favors the alignment of chromosomes along the equatorial plate?
a. Centromere duplication
b. Puling and pushing of the spindle fiber
c. The presence of centrosome
d. The pair of aster at the beginning of cell division

6. Which of the following is the main feature of anaphase?

a. The separation of sister chromatids towards the opposite pole
b. The start of cytokinesis
c. The formation of cleavage furrow in the cell
d. The alignment of chromosomes in the equatorial plate

7. Which of the following proteins served as checkpoints in each stage of Interphase?

a. Ketose and Kinases c. Cyclins and Histones
b. Kinases and Cyclins d. Histones and Kinases
8. How is a chromosome different from a chromatin?
a. A chromosome is a segment of DNA while chromatin is the DNA itself
b. A chromatin is a segment of DNA while chromosome is the DNA itself
c. Chromosome is tightly coiled DNA while chromatin is loosely coiled DNA
d. Chromatin is tightly coiled DNA while chromosome is loosely coiled DNA

9. Which of the following term produces the spindle fibers which pulled the sister chromatids
towards the opposite poles?
a. Centriole c. Centrosome
b. Centromere d. Asters

10. Why is there a need to produce diploid type of cell at the end of cell division?
a. so that the cells produced are exact copy of the parent cell
b. So that abnormalities of the cell will be avoided.
c. So that the purpose of growth happens in the organism
d. So that the copy of DNA is retained.

11. Which of the following is the main reason why DNA must exist in chromosome form?
a. To favor the formation of sister chromatids
b. To allow the protein histones to carry out its task
c. To avoid the genetic material to be tangled away during cell division
d. To promote the formation of spindle fibers

12. A cell with a diploid number of 24 undergoes meiosis, how many chromosomes are in each
daughter cell?
a. 6 b. 12 c. 24 d. 48

13. Meiosis results in ______.

a. 2 haploid daughter cells c. 2 diploid daughter cells
b. 4 haploid daughter cells d. 4 diploid daughter cells

14. Which of the following cells undergo meiosis?

a. sperm cells c. unicellular organisms
b. liver cells d. all of these

15. Crossing over occurs during

a. Anaphase 1
b. Metaphase 2
c. Prophase
d. Prophase