The Eukaryotic Cell Cycle and Cancer

In Depth Click & Learn

Student Worksheet

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.
Cell divison is the only way for unicellular organisms can reproduce, while multicellular
organisms use cell divison 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.
So unhealthy, unnecessary, or damaged cells are removed which could be harmful organism.

3. What is the role of growth factors?

Growth factors--small proteins that circulate in the bloodstream--stimulates signals inside
cells that cause G 1-phase cyclin concentrations to rise. The cyclins bind to the appropriate
CDKs, which then phosphorylate other proteins to drive the cell cycle into S phrase.
4. Cells divide, differentiate, or die. What is differentiation?
Differentation is when cells stop dividing to specialiaze in structure and function.

5. What is apoptosis? Explain its purpose.

Apoptosis is programmed cell death, which is meant to eliminate unnecessary cells during
development and removes unhealthy or damaged cells in the mature organism.

6. Organisms maintain the right number of cells by regulating the cell cycle. What are “cell cycle regulators?”
Cell cycle regulators are molecular signals that may stimulate or halt cell division, which
instructs cells to differentiate, or initiate cell death.

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: The crypt

Cell Differentiation: The crypt

Apoptosis: Top of the villus

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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.

Warts and 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. Growth--> G1

b. DNA Replication--> Synthesis (S)

c. Preperation to divide-- G2

d. Division--> Mitosis (M)

11. In general, what is the purpose of a checkpoint in the cell cycle?

To regulate the progression from one phase of the cell cycle to the next.

12. What is one potential outcome when errors occur in this highly regulated cell cycle process?
One outcome is the development of cancer.

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 ______________________________________
cyclin-dependent kinases .
16. What is a kinase, and what does it do?
Kinases are enzymes that add a phosphate to other proteins to activate or inhibit their
function--a process known as phosphorylation.

17. When are CDKs present inside the cell during the cell cycle?
CDKs are always present in the cell but become active only when they are bound to other
proteins called cyclins.
18. When are cyclins present inside the cell during the cell cycle?
Cyclins, whose concentration inside the cell cycles up and down, depending on the phase of
the cycle.
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The Eukaryotic Cell Cycle and Cancer – In Depth Student Worksheet
19. CDKs form molecular complexes with cyclins. What do activated CDK-cyclin complexes do?
They 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

1)Growth factors promote G1-phase
The newly divided cell Confirm that there cyclin expression.
enters this phase is no DNA damage 2)G1-phase cyclins accumulate
right after completing Confirms that there activatibg the CDK-cyclin, allowing
cell division. are sufficient it to phosphorylate target proteins
that ultimately promotes the cell's
G1 During G1, the cell
resources to proceed transition to S phase.

increasesin size ad through cell divsion. if the DNA is damaged, p53 will
inhibit the G1 CDK-cyclin complex
prepares to replicate preventing the cell from leaving G1
until the damage is repaired or it
its DNA. di

1) Growth factors promote S-phase

The cell replicates Confirms that cyclin expression.
its DNA there are no 2) S-phase cyclins accumulate
activating the S-phase CDK-cyclin
At the end, cell has errors in the complex that promotes DNA
replication
S 2 complete sets of replicated DNA
If DNA damage is identified,
chromosomes specific proteins (e.g. tumor
suppressor genes ataxia
telangiectasia mutated (ATM) and
Breast Cancer 1 (BRCA1)) recognize
and inhibit cell cycle progressio

Confirms that the DNA is 1) M-phase cyclin expression.

The cell not damged 2) M phase cyclins accumulate
continues activating the M-phase CDK-cyclin
Confirms that there are 2 complex that promotes DNA
cellular growth complete sets of
replication

G2 in preparation chromosomes If DNA is damaged, tumor

suppressor genes (such as p53) will
for division Confirms that there
inhibit the CDK-cyclin complex
preventing the G2-M phase
enough cellular transition until the damage is
components for 2 daughter repaired or the cell dies.
cells
M-phase CDK-cyclins activate the anaphase-promoting
The cell stops -Checks if any complex/cyclosome (APC/C) once all of the chromosomes
are attached to the mitotic spindle. Once active,
growing sister
the APC/C allows the proteins holding the sister
chromatids together to be degraded and the chromatids
to be separated to opposite sides of the cell during
anaphase.

The cell divides chromatids are

M
If the chromosomes are not properly attached to the
mitotic spindle, the mitotic arrest deficient (MAD)

into 2 daughter attached to protein inhibits the APC/C preventing transition to

(mitosis)
anaphase

cells, each with the mitotic spinddle

same number of
chromosomes

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?
G1,S, and G2 make up intyerphase: the period during which a cell grows and replicates its DNA. A dividing cells
repeatedly cycles through interphase and mitosis; in other words, it goes througj cycles of growth and division.

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?
The organism's stage in development, the type of cell, and the resources available.

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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.
Neurons and muscle cells
a.

b. Liver tissues when injury causes the cell to leave G0 and progress through the cell cycle
to divide.
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.
One reason is too muich cell division, the other is too little cell death.

24. What causes uncontrolled cell division at the genetic level?

Uncontrolled division of cells is caused by mutations affecting 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.
The cells fail to differentiate and pile up rather than exiting the crypt resulting in tumor
formation.
26. Normally, proto-oncogenes stimulate the cell cycle. What do mutated proto-oncogenes (i.e., oncogenes)
cause?
Mutated proto-oncogenes stimulate cell division causing uncontrolled cell division.

27. Normally, tumor suppressor genes inhibit the cell cycle. What do mutated tumor suppressor genes cause?
The muttaion in the tumor suppressors causes a loss of inhibition, which leads tro uncontrolled
cell division.
28. To cause cancer, proto-oncogenes require ___ 1 (or) ___ 2 allele(s) to be mutated and are therefore
1 allele

considered ___ loss

tick dominant (or) ___ recessive. This results in a ___________ of function.

29. To cause cancer, tumor suppressor genes require ___ 1 (or) tick
___ 2 allele(s) to be mutated and are therefore
considered ___ dominant (or) tick
___ 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.
A proto-oncogene is always serving as a go signal pushing on the gas to promote the cell
cycle. When even a single copy/allele for that gene is mutated becoming an oncogene, the
gas pedal is depressed further increasing the rate of the cell cycle
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.
When one copy/allele for such a gene is lost, the brake pedal remains depressed by the single
functioning copy. However, when both alleles are lost, the brake is no longer depressed, and
only then can the cell cycle can proceed.

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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.”

b. Explain what happens to the cell cycle if both alleles of the gene encoding p53 are mutated.

32. Explain why people who inherit one mutated allele of the BRCA1 gene have a higher likelihood of
developing cancer.

33. Predict a potential outcome of a mutated mitotic arrest deficient (MAD) protein.

34. Use the model illustrated in the figure below to answer the accompanying questions.

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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.

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?

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.

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