Click & Learn

Student
Worksheet
The Eukaryotic Cell Cycle and Cancer
In Depth

INTRODUCTION

This handout complements the Click & Learn The Eukaryotic Cell Cycle and Cancer and is intended as an in
depth examination of the cell cycle and the protein players involved. For a more general overview, please see
the overview version.

PROCEDURE
Follow the instructions as you proceed through the Click & Learn and answer the questions in the spaces below.

Click on the “Background” tab on the right side.

1. Compare and contrast the reasons cell division is important for unicellular (single-celled) and multicellular
organisms. Only way single-celled organisms can reproduce but also multicellular organisms need cell
division to grow and replace dead or damaged cells

2. Provide an example of why cell division remains important to an adult organism even after it is fully

developed. Cell division is still crucial in healing wounds like skin cuts or broken bones

3. What is the role of growth factors? In response to molecular signals sent from growth factors, cell division
occurs

4. Cells divide, differentiate, or die. What is differentiation? When cells become specialized in structure and
function, this process is called cell differentiation.

5. What is apoptosis? Explain its purpose. Programmed cell death, eliminates unnecessary cells during
development and also removes unhealthy/damaged cells in mature organisms

6. Organisms maintain the right number of cells by regulating the cell cycle. What are “cell cycle regulators?”
These are molecular signals that either stimulate or stop cell division and signal the cell to start differentiation,
or apoptosis.
 7. Watch the video clip of cells in the small intestine. Name the general location along the villus where the

following processes occur:

Cell Division: intestinal crypts

Cell Differentiation: At the crypt, along the lumen

Apoptosis: crypt at the level of stem (top level)

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Click & Learn The Eukaryotic Cell Cycle and Cancer – In Depth Student Worksheet

8. Name one harmless result of too little cell division. Hair loss

9. Name one harmless result of too much cell division. Tumors

Click on the section of the circle labeled “Cell Cycle Phases” in the center purple circle on the right and use

the “Overview” information in the window on the left to answer the questions below.
10. List, in order, the four events we collectively call the “cell cycle.” Next to each event, write the correlating
cell cycle phase name.

a. G1

b. S

c. G2

d. M

11. In general, what is the purpose of a checkpoint in the cell cycle? These checkpoints look for any errors that
might occur to the DNA or the overall process of cell division, and they make sure the progression of the process
is smooth and without any error.

12. What is one potential outcome when errors occur in this highly regulated cell cycle process?
Development of cancerous cells

Click on “Cell Cycle Regulators and Cancer” in the center purple circle on the right. Use the information under
 “Regulators Overview” in the window on the left to answer the questions below.

13. What type of protein that regulates the cell cycle is encoded by proto-oncogenes? Stimulating proteins

14. What type of protein that regulates the cell cycle is encoded by tumor suppressor genes? Inhibitory proteins

15. The most important cell cycle regulators are the

____CDK’s__________________________________ .
16. What is a kinase, and what does it do? Enzymes that phosphorylate other proteins to activate or inhibit their
function

17. When are CDKs present inside the cell during the cell cycle? Always present, but only active when they are
bound to other proteins called cyclins

18. When are cyclins present inside the cell during the cell cycle? Concentration of different CDK-cyclins goes up
and down depending on the phase of the cycle

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Click & Learn The Eukaryotic Cell Cycle and Cancer – In Depth Student Worksheet

19. CDKs form molecular complexes with cyclins. What do activated CDK-cyclin complexes do? Stimulate the cell
cycle

Using the cell cycle diagram on the right and both links in the center purple circle, complete the table below
for each phase. Use bullet points and focus on major events that occur during each phase, checkpoint, and

regulatory process. Complete the entire row before moving on to the next phase.
PHASE PHASE EVENTS CHECKPOINT EVENTS REGULATORY PROCESSES

G1 -​ Newly divided -​ Cell has to be

CDK-cyclins drive cells
cell enters this sufficiently
through G1 and into S phase.
phase after healthy to
Growth factors stimulate
completing replicate its DNA signals inside cells causing the
mitosis -​ If so, growth cyclin concentration to
-​ Cell increases in signals will increase. The cyclin then binds
size and prepares stimulate the cell to the CDK and
to replicate its to proceed to the phosphorylation occurs
 DNA S phase
-​ If not, it enters
the resting phase, If DNA is damaged, p53
G0 protein stops the progression
-​ No DNA damage, into S phase by inhibiting
Sufficient CDK-cyclin. Retinoblastoma
protein (Rb) prevents cells
resources
from entering S phase in the
absence of signals from
growth factors. The genes that
encode p53 and Rb are known
as Tumor suppressor genes, as
they prevent the development
of tumors by keeping cell
division in check

S Cell replicates its DNA, at Summary: No errors

Once the concentration
the end of the phase the during DNA replication,
of S-Phase cyclins reach a
cell has two complete
threshold, CDK-cyclins signal
sets of chromosomes. the cell to duplicate the DNA.
Growth factors usually
stimulate the rise in S-Phase
cyclin concentration

Breaks in the two DNA

strands activates ATM protein,
which halts the cell cycle and
activates proteins for repairing
the DNA strand. Breast Cancer
1 (BRCA1) interacts with a
series of proteins to mediate
either DNA repair or
apoptosis.

G2 Second Gap Phase: Cell Checklist:

Concentration of Mitotic
continues to grow and DNA without damage
cyclins rises, and they bind to
prepares for division Chromosomes set
appropriate CDKs. If there is
complete DNA damage or incomplete
Enough cell components replication, inhibitory proteins
prevent the activation of
CDK-cyclin.

If DNA is damaged, p53

proteins will stop the cell cycle
until damage is repaired. If
damage is excessive p53
initiates apoptosis.
 M Cell stops growing, and Checklist:
(mitosis) M-phase cyclins and CDKs
divides into two daughter
activate a protein complex
cells each with the same -​ All sister
known as
number of chromosomes. chromatids are Anaphase-promoting
attached to complex/cyclosome (APC/C).
mitotic spindle The Active APC/C stimulates
the destruction of proteins
that hold the two companies
of each chromosome together
at the centromere, allowing
chromatids to separate during
anaphase.

Mitotic arrest deficient

(MAD) proteins are stimulated
when sister chromosomes are
not properly attached to the
mitotic spindle, and as a result
inhibit APC/C, preventing the
entry to anaphase.

20. Go to “Cell Cycle Phases” and click on “Interphase.” The interphase alternates with mitosis. What happens
during interphase and what phases does it include? During interphase, the cell grows, replicates its DNA
and gets ready for mitosis (includes G1, S, G2).

21. Go to “Cell Cycle Phases” and click on “G0.” The G0 phase is a resting or nondividing stage. What three
factors determine if a cell enters G0? Organisms stage in development, type of cell, and resources
available

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Click & Learn The Eukaryotic Cell Cycle and Cancer – In Depth Student Worksheet

22. Provide an example of a fully differentiated cell that is (a) permanently in G0 and (b) one that can leave G0

to progress through the cell cycle and divide again.

a. neurons

b. Liver cells

Click on “Cell Cycle Regulators and Cancer” in the center purple circle on the right. Then click on the “Cancer
Overview” tab in the window to the left (right tab).
23. Cancer is an improperly regulated cell cycle. Name two reasons why cells can form tumors.

Too much or too little cell division

24. What causes uncontrolled cell division at the genetic level? Mutations that impact proteins that normally
regulate the cell cycle.

25. Watch the video clip. At the cellular level in this example, explain what occurs if the APC gene is mutated.
When APC gene is mutated, it has trouble finalizing differentiation in the last part and it piles up (forming
tumors)

26. Normally, proto-oncogenes stimulate the cell cycle. What do mutated proto-oncogenes (i.e., oncogenes)

cause? They increase stimulation to a greater extent and therefore lead to uncontrolled cell division

27. Normally, tumor suppressor genes inhibit the cell cycle. What do mutated tumor suppressor genes cause?
Cause loss of inhibition and leads to uncontrolled cell division

28. To cause cancer, proto-oncogenes require ___ 1 (or) ___ 2 allele(s) to be mutated and are therefore
considered ___ dominant (or) ___ recessive. This results in a ___override________ of function.

29. To cause cancer, tumor suppressor genes require ___ 1 (or) ___ 2 allele(s) to be mutated and are therefore
considered ___ dominant (or) ___ recessive. This results in a _____loss______ of function.

30. Watch the video clip.

a. Using the gas pedal analogy, explain the impact on the cell cycle of a proto-oncogene versus an
oncogene. Oncogene usually stimulates the cell cycle however proto-oncogenes which are
mutated oncogenes rather increase the simulation to a high extent similar to putting one's
foot on a gas pedal, this in the molecular level leads to uncontrolled cell division.

b. Using the brake pedal analogy, explain the impact on the cell cycle of one mutated tumor suppressor

gene allele versus two mutated tumor suppressor alleles. The suppressor genes are like brake pedals and
inhibit the cell cycle but when mutated the 2 alleles cause loss of inhibition and function as if removing
your foot from the brake pedal, ultimately lead to the formation of tumor
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Click & Learn The Eukaryotic Cell Cycle and Cancer – In Depth Student Worksheet

ADVANCED EXTENSION QUESTIONS (OPTIONAL)

Now that you have finished the Click & Learn, use your knowledge to answer the following questions.
31. p53 is a protein that is encoded by a tumor suppressor gene, and some scientists refer to it as “the

guardian of the genome.”

a. Explain its normal role and why scientists would regard it as the “guardian of the genome.”
Due to its role in being essential for regulating cell division ( as seen in the checkpoint in G1
and G2) phase but also p53 regulates DNA repair.

b. Explain what happens to the cell cycle if both alleles of the gene encoding p53 are mutated. Cell cycle
becomes uncontrolled especially the checkpoints at G1 and G2 phase which rely on p53 for making sure that
DNA replication is accurate and the cell is ready for division, and with a mutated p53, tumor production will
result.

32. Explain why people who inherit one mutated allele of the BRCA1 gene have a higher likelihood of
developing cancer. Because the BRCA1 gene plays an important role in the S phase to wor with
other proteins as a way of performing DNA repair and apoptosis in case the damage to the
DNA is excessive. With a mutated BRCA1 gene, the cell loses the tumor suppressor gene
regulating the damages done to DNA so a higher chance of developing cancer results.

33. Predict a potential outcome of a mutated mitotic arrest deficient (MAD) protein. During mitosis, the
checkpoints are unable to detect chromosomes that are not attached to the mitotic spindle during metaphase
and wrongly let the cell enter anaphase which results to genetic disorders such as down syndrome

34. Use the model illustrated in the figure below to answer the accompanying questions.
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Click & Learn The Eukaryotic Cell Cycle and Cancer – In Depth Student Worksheet

a. The human gene EGFR located on chromosome 7 is a proto-oncogene that codes for a growth factor

cell surface receptor. The binding of growth factors to this receptor can lead to cell proliferation.
Hypothesize what potential impact a mutated EGFR allele will have on a cell. Give one possible
impact

and explain your answer. Uncontrolled cell proliferation, causing the receptor to be active without
growth factor binding, results in excessive cell division and cancer formation

b. RAS is a G protein that is activated when a growth factor attaches to EGFR. Its activation results in the
exchange of GTP for GDP. Once activated, the GTP cannot be hydrolyzed and RAS cannot be deactivated
What is one potential outcome of a mutation in one of the two copies of RAS? Uncontrolled cell growth
and cell proliferation leading to the development of malignant cells

c. Mutations in the genes that code for proteins in this pathway have been linked to various types of

cancer (i.e., RAS: pancreatic, BRAF: colorectal, MEK: melanoma, EGFR: lung). If you were developing a

new cancer drug, what would be an appropriate target protein for the new drug therapy? Justify
your answer. Proteins that directly target the specific type of cancer, such as MEK
(mitogen-activated protein kinase)

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