Chapter 18—Cell-Cycle Regulation and the Genetics of Cancer
Fill in the Blank
1. Mutations in the RB gene have been linked to inheritance between generation of some
types of cancers. A mutation in RB is dominant for _____________________ cancer in
individuals, while a mutation in RB is recessive for ___________________ cancer in
individual cells.
Ans: susceptibility to, expression of (or progression to)
Difficulty: 3
2. Researchers have isolated cell-cycle-defective, temperature sensitive mutants in which a
protein needed for cell division functions normally at a _____________________
temperature but loses function at a higher ______________________ temperature.
Ans: permissive, restrictive
Difficulty: 3
3. An enzyme converts a ___________________________ to a
_______________________ .
Ans: substrate, product
Difficulty: 3
4. _________________________________ kinases control the cell cycle by
phosphorylating other proteins.
Ans: cyclin-dependent
Difficulty: 3
5. An arrest in the cell cycle for repair is called a ____________________.
Ans: check point
Difficulty: 3
6. An increase from the normal two copies to hundreds of copies of a given gene indicates
gene ________________________ has occurred.
Ans: amplification
Difficulty: 3
7. During ____________________, or programmed cell death, DNA is degraded and the
nucleus condenses in a response to the presence of DNA damage.
Ans: apoptosis
Difficulty: 3
8. _________________ factors are extracellular hormones and cell-bound signals that
stimulate or inhibit cell proliferation.
Ans: growth
Difficulty: 3
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9. Mutant alleles that act dominantly with respect to a cancer phenotype are called
_________________.
Ans: oncogenes
Difficulty: 3
Multiple Choice
10.
A)
B)
C)
D)
E)
DNA replication occurs during ______ of the cell cycle.
prophase
G1 phase
S phase
G2 phase
mitosis
Ans: C
Difficulty: 1
11.
A)
B)
C)
D)
E)
Which of the following does not occur during mitosis?
Segregation of sister chromatids.
Duplication of chromosomal DNA.
Condensation of chromosomes.
Nuclear envelope breakdown.
Attachment of chromosomes to mitotic spindle.
Ans: B
Difficulty: 2
12. The yeast Saccharomyces cerevisiae is particularly useful for genetic analysis of cell
cycle control because:
A) it is prokaryotic, allowing it to divide rapidly.
B) mutant yeast cells form cancerous tumors.
C) reproduction by budding allows easy identification of stage in cell cycle.
D) all cells in a culture remain at the same stage of the cell cycle.
E) yeast cells lack G1 and G2 stages.
Ans: C
Difficulty: 3
13. The yeast Saccharomyces cerevisiae reproduces _______________, allowing easy
determination of the cell cycle stage in which a cell is found.
A) ambiguously
B) by fission
C) sexually
D) amorphously
E) by budding
Ans: E
Difficulty: 1
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14. In the cell cycle of Saccharomyces cerevisiae, the appearance of a bud on the surface of
a cell indicates that the cell:
A) is entering M phase.
B) has a mutation in a gene regulating G2M transition.
C) is haploid.
D) has a mutation in a gene regulating G2S transition.
E) reaching the end of G1 phase.
Ans: E
Difficulty: 2
15. The temperature at which a cell with a temperature-sensitive mutation is unable to
survive is considered the ___________ temperature.
A) restrictive
B) mutant
C) dissociative
D) permissive
E) alternative
Ans: A
Difficulty: 1
16. The cells in a population of yeast cells in which all members of the population have a
temperature-sensitive mutation in the same gene involved in cell cycle progression will
appear _________ when shifted to the restrictive temperature.
A) to vary in morphology
B) as clumps of lysed cells
C) to adhere to each other
D) uniform in size and shape
E) arrested in all stages of the cell cycle
Ans: D
Difficulty: 3
17. The ________ gene controls progression through “start” at the end of G1 in the cell
cycle.
A) CDK
B) RAS
C) CDC28
D) RAD9
E) DCC
Ans: C
Difficulty: 3
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18.
A)
B)
C)
D)
E)
Enzymes that covalently link phosphate groups to their substrates are termed:
kinases.
phosphatases.
cyclins.
phosphatase inhibitors.
ligases.
Ans: A
Difficulty: 2
19. CDKs, such as CDC28, require the assistance of ____________ to carry out their
enzymatic activity.
A) restriction enzymes
B) proteases
C) nucleases
D) growth factors
E) cyclins
Ans: E
Difficulty: 2
20. ________________ are proteins that form a structural scaffold on the inner surface of
the nuclear membrane.
A) Mitotic tubules
B) Nuclear lamins
C) Chromatin fibrils
D) CDKs
E) Histones
Ans: B
Difficulty: 2
21.
A)
B)
C)
D)
E)
The solubility of nuclear lamins is regulated by the _____________ of lamin proteins.
length
phosphorylation state
kinase activity
molecular weight
condensation
Ans: B
Difficulty: 3
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22. The retinoblastoma (Rb) protein regulates progression into S phase by regulating
___________ activity.
A) cyclin D
B) p53
C) CDK4
D) E2F
E) CDC28
Ans: D
Difficulty: 3
23.
A)
B)
C)
D)
E)
The activity of Rb is regulated by:
its phosphorylation state.
cyclin A.
E2F.
its polyA tail.
its level of methylation.
Ans: A
Difficulty: 2
24.
A)
B)
C)
D)
E)
The ____________ checkpoint is disrupted by mutations that alter p53 function.
G0-to-G1
G1-to-S
S-to-G2
G2-to-M
M-to-G1
Ans: B
Difficulty: 3
25.
A)
B)
C)
D)
E)
Which of the following is not likely to result form the loss of functional p53?
The appearance of homogenously staining regions on chromosomes.
Increases propensity to arrest in G1.
Alterations in the G1 to S checkpoint.
An increase in gene amplification in affected cells.
Generation of fragments of chromosomal DNA lacking telomeres and centromeres.
Ans: B
Difficulty: 3
26.
A)
B)
C)
D)
E)
A programmed cell change that results in cell death is referred to as:
apoptosis.
G1 regulation.
post-translational control.
cancer.
metastasis.
Ans: A
Difficulty: 2
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27. Damage to DNA that takes place during DNA replication results in arrest of normal
cells at the _______________ checkpoint.
A) G0-to-G1
B) G1-to-S
C) S-to-G2
D) G2-to-M
E) M-to-G1
Ans: D
Difficulty: 4
28. The cell-cycle checkpoint that occurs during mitosis causes nuclear division to pause
until:
A) DNA replication is complete.
B) sister chromatids have separated.
C) cytokinesis occurs.
D) telophase begins.
E) all chromosomes have attached to the mitotic spindle.
Ans: E
Difficulty: 3
29. CDKs associate with cyclins at specific stages of the cell cycle. The CDK subunit is
responsible for phosphorylating a substrate protein, while the cyclin is responsible for:
A) progression into G0.
B) degradation of the CDK after phosphorylation.
C) ubiquitin function.
D) dephosphorylating Rb.
E) determining which specific proteins will be phosphorylated.
Ans: E
Difficulty: 3
30. Which of the following is not a common consequence of mutations that eliminate cellcycle checkpoints?
A) Increased DNA damage
B) Decreased frequency of cell division
C) Polyploidy
D) Aneuploidy
E) Increased chromosome loss
Ans: B
Difficulty: 3
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31. Molecules that function to stimulate or inhibit cell division are collectively referred to
as:
A) transcription factors.
B) polymerases.
C) kinases.
D) growth factors.
E) checkpoints.
Ans: D
Difficulty: 2
32. _______________________ are proteins that span the plasma membrane and transmit
signals from outside the cell into the cytoplasm.
A) Receptors
B) Transcription factors
C) Growth factors
D) Nucleosomes
E) Polymerases
Ans: A
Difficulty: 2
33.
A)
B)
C)
D)
E)
Cytoplasmic proteins that relay signals inside the cell are referred to as:
growth factors.
signal transducers.
receptors.
transcription factors.
polymerases.
Ans: B
Difficulty: 2
34.
A)
B)
C)
D)
E)
In its active form, the RAS protein is associated with:
DNA.
ATP.
GTP.
RNA.
GDP.
Ans: C
Difficulty: 3
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35. The generation of a cancerous cell requires mutations in ____________ of that cell's
genes.
A) none
B) one
C) two
D) 5-10
E) more than 100
Ans: D
Difficulty: 1
36. All cells in a cancerous tumor arise from a single mutant precursor cell, meaning that
the cells in the tumor are:
A) sporadic.
B) spastic.
C) benign.
D) divisionary.
E) clonal.
Ans: E
Difficulty: 3
37.
A)
B)
C)
D)
E)
Which of the following statements regarding cancer is true?
All cancers are genetic.
All cancers are sporadic.
All cancers run in families.
None of the above
a, b, and c
Ans: A
Difficulty: 2
38. ______________________ are mutant forms of normal genes that act dominantly to
predispose a cell to a cancerous phenotype.
A) Polymerases
B) Oncogenes
C) Activators
D) Tumor suppressors
E) Proto-oncogenes
Ans: B
Difficulty: 2
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39. Genes whose mutant alleles can function in a recessive manner to predispose cells to
cancerous growth are referred to as:
A) polymerases.
B) oncogenes.
C) activators.
D) tumor suppressors.
E) proto-oncogenes.
Ans: D
Difficulty: 1
40. The human papilloma virus (HPV) carries a gene that functions as an oncogene by
inactivating the p53 protein. The fact that the loss of p53 function is oncogenic suggests
that:
A) p53 normally functions to prevent uncontrolled cell division.
B) The HPV protein is encoded by a tumor suppressor gene.
C) p53 gene expression is upregulated by the HPV protein.
D) The HPV protein functions at origins of replication on DNA.
E) p53 is a proto-oncogene.
Ans: A
Difficulty: 4
41.
A)
B)
C)
D)
E)
Some oncogenic forms of the RAS protein are oncogenic because they are unable to:
convert GDP to dGDP.
associate with GTP.
release ATP.
hydrolyze GTP to GDP.
convert ADP to ATP.
Ans: D
Difficulty: 4
42. Genes encoding which of the following protein types do not function as oncogenes
when mutated?
A) transmembrane receptors
B) transcription factors
C) signal transmitters
D) growth factors
E) tumor suppressors
Ans: E
Difficulty: 3
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43.
A)
B)
C)
D)
E)
Normal alleles of tumor suppressor genes function to encode proteins that:
promote transition from G1-to-S.
can slow the rate of cell division.
increase the rate of mutagenesis.
activate oncogenes.
associate with growth factors at the cell surface.
Ans: B
Difficulty: 1
44. Tumor cells removed from an individual with retinoblastoma are _________________
for a deletion of the RB gene.
A) homozygous
B) heterologous
C) hemizygous
D) heterozygous
E) endozygous
Ans: A
Difficulty: 2
45. Which of the following does not function to reduce the likelihood of a cell becoming
cancerous?
A) Alternative splicing within the nucleus
B) Mismatch repair enzymes
C) Proofreading ability of DNA polymerases
D) Cell cycle checkpoints
E) Tumor suppressor genes
Ans: A
Difficulty: 3
46.
A)
B)
C)
D)
E)
Cells that have migrated from a tumor and invaded a distant tissue are said to have:
acclimated.
metastasized.
mutagenized.
carcinogized.
capacitated.
Ans: B
Difficulty: 1
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47. Glioblastoma multiforme (GBM) is an aggressive cancer caused by alterations in
_________________ in the brain.
A) arteries
B) neurons
C) glial cells
D) mitochondria
E) lymphocytes
Ans: C
Difficulty: 1
48.
A)
B)
C)
D)
E)
Glioblastoma multiforme (GBM) results from mutations in genes encoding:
proto-oncogenes.
tumor suppressors.
cell cycle inhibitors.
a and c
a, b, and c
Ans: E
Difficulty: 2
49. Alterations in the activity of cyclin-dependent kinases can affect the _____________
cell cycle checkpoint.
A) G1-to-S
B) S-to-G2
C) G2-to-M
D) a or c only
E) a, b, or c
Ans: D
Difficulty: 1
50. _____________________ are enzymes that function to promote or inhibit cell cycle
progression by phosphorylating specific substrates.
A) Cyclins
B) Growth factors
C) Mutagens
D) Cyclic phosphatases
E) Cyclin dependent kinases
Ans: E
Difficulty: 2
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51. ______________________ are proteins that assist in regulating cell cycle progression
and are often rapidly degraded at specific times in the cell cycle.
A) Cyclins
B) Growth factors
C) Mutagens
D) Receptors
E) Cyclin dependent kinases
Ans: A
Difficulty: 2
52. Cyclin dependent kinases require _______________________ to catalyze
phosphorylation of appropriate substrate proteins.
A) cyclins
B) growth factors
C) mutagens
D) receptors
E) aneuploidy
Ans: A
Difficulty: 2
53.
A)
B)
C)
D)
E)
Genetic testing for cancer can:
identify individuals that are resistant to cancer.
indicate increased risk for certain cancers.
predict the age of cancer onset in an individual.
eliminate the possibility that an individual will develop cancer.
none of the above
Ans: B
Difficulty: 1
54.
A)
B)
C)
D)
E)
Which of the following functions to regulate the G2-to-M transition?
cyclin A
cyclin B
cyclin C
cyclin D
cyclin E
Ans: B
Difficulty: 3
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55. In Saccharomyces cerevisiae, the _________________ protein inhibits progression of
the cell cycle into mitosis in response to DNA damage.
A) p53
B) RAD9
C) Rb
D) E2F
E) CDK
Ans: B
Difficulty: 2
56. Proteins produced from tumor suppressor genes function as _____________________
regulators of cell cycle progression.
A) proto-oncogenic
B) positive
C) mutant
D) non-functional
E) negative
Ans: E
Difficulty: 2
57. Oncogenes found in viral genome often cause _____________________ when
incorporated into eukaryotic cells.
A) cell death
B) arrest in G0
C) increased cell proliferation
D) arrest at the G2-to-M checkpoint
E) apoptosis
Ans: C
Difficulty: 1
58. One characteristic of cancer is unregulated cell proliferation. A second characteristic of
cancer cells is:
A) the synthesis of additional copies of DNA polymerase.
B) arrest in G0.
C) the failure to expand clonally.
D) apoptosis.
E) the ability to migrate to distant tissues.
Ans: E
Difficulty: 2
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59. The point in the cell cycle at which a cell is committed to progression from G1 phase
into S phase is termed:
A) M.
B) CDC28.
C) G0.
D) Start.
E) Ontogeny.
Ans: D
Difficulty: 2
Matching
Using the cell stages listed, indicate the stage in the cell cycle in which each event occurs in
eukaryotic cells
a. G0
b. G1
c. G2
d. M
e. S
60. Cyclin A association with CDKs.
Ans: e
Difficulty: 3
61. Formation of CDK4/cyclin D complexes.
Ans: b
Difficulty: 2
62. DNA replication.
Ans: e
Difficulty: 1
63. Initial bud formation in Saccharomyces cerevisiae.
Ans: b
Difficulty: 2
64. Preparation for nuclear division.
Ans: c
Difficulty: 1
65. Chromosome segregation.
Ans: d
Difficulty: 1
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66. Preparation for duplication of DNA.
Ans: b
Difficulty: 2
67. Lamin dephosphorylation.
Ans: d
Difficulty: 3
68. Chromosome condensation.
Ans: d
Difficulty: 2
69. Cell cycle arrest in S. cerevisiae CDC28 mutants.
Ans: b
Difficulty: 2
70. Repair of DNA damaged by single-strand nicking.
Ans: b
Difficulty: 3
71. Formation of CDK2/cyclin E complexes.
Ans: b
Difficulty: 4
72. Phosphorylation of Rb protein.
Ans: b
Difficulty: 3
73. Formation of CDC2/cyclin B complexes.
Ans: c
Difficulty: 4
True or False
74. The cell cycle has four phases, G, S1, S2, and M.
Ans: False
Difficulty: 2
75. Of the approximately 300 cell types, some, once terminally differentiated, never divide
again even if life continues for nearly a century.
Ans: True
Difficulty: 1
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76. The S phase is when sister chromosomes segregate into daughter cells.
Ans: False
Difficulty: 2
77. A temperature sensitive screen is completed by treating cells with mutagen, replica
plating, and then selecting for growth in permissive and restrictive temperatures.
Ans: True
Difficulty: 1
78. Cyclin-dependent kinases together with cyclins control the timing of cell-cycle events.
Ans: True
Difficulty: 1
79. Cell-cycle check points are arrests to the cell cycle in which the integrity of the genome
and cell-cycle machinery are “checked” prior to continuing to the next cell-cycle stage.
Ans: True
Difficulty: 1
80. As cells begin DNA replication in the S phase, cyclin A is degraded and cyclins D and E
are synthesized.
Ans: False
Difficulty: 2
81. An enzyme that removes a phosphate group from proteins is called a phosphatase.
Ans: True
Difficulty: 1
82. DNA damage activates the p53 transcription factor, which in turn induces expression of
the p21 gene.
Ans: True
Difficulty: 1
83. DNA damage in normal cells only rarely leads to apoptosis.
Ans: False
Difficulty: 2
Short Answer
84. The cells in a cancerous tumor are described as being “clonal.” What does this mean?
Ans: All cells in the tumor are descendants of a single precursor cell.
Difficulty: 2
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85. Cell-surface receptors function to transmit signals from the outside of the cell into the
cytoplasm. Name the three protein domains that are responsible for receptors to
accomplish this signal transmission.
Ans: Signal-binding site, transmembrane domain, and intracellular signal transmission
domain.
Difficulty: 3
86. You have generated a novel mutation in a strain of S. cerevisiae, and you designate this
mutation CDC90 because the mutated gene appears to encode a protein that functions in
regulating cell cycle progression. Interested in studying the CDC90 mutation further,
you obtain a CDC28 mutant yeast strain from a colleague and observe that the CDC90
and CDC28 mutant strains exhibit different phenotypes. How could you determine if
one of these mutations functions upstream from the other in controlling progression of
yeast cells through the cell cycle?
Ans: Generate a mutant yeast strain that contains both the CDC28 and CDC90
mutations and perform epistatic analysis. If the double mutant has the phenotype
of one of the mutations, then that mutation is epistatic and is upstream in the
pathway.
Difficulty: 4
87. Name two mechanisms by which a retrovirus carrying a proto-oncogene can convert to
proto-oncogene to an oncogene.
Ans: A mutation can occur in the viral genome that alters the sequence of the protooncogene itself, thus generating an oncogene. Or, the proto-oncogene can be
inserted adjacent to a strong promoter, resulting in overexpression of the gene.
Difficulty: 3
Define (Provide a two- or three- sentence definition or description of the following terms or
genes)
88. Proto-oncogene
Ans: Normal gene regulating cell proliferation that can become an oncogene when
mutated.
Difficulty: 2
89. Apoptosis
Ans: Programmed cell death in which the cell coordinates its own DNA degradation
and nuclear condensation.
Difficulty: 3
90. CDK
Ans: Cyclin-dependent kinase. A family of proteins that phosphorylate specific
substrates in response to a cell-cycle dependent association with specific cyclins.
Difficulty: 2
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91. Signal transduction
Ans: The relaying of a signal through the cytoplasm to the nucleus in order to mediate a
cellular response to an extracellular signal.
Difficulty: 3
92. Oncogene
Ans: Mutant allele of a proto-oncogene that acts dominantly to promote a cancerous
phenotype.
Difficulty: 2
93. RB
Ans: Retinoblastoma tumor suppressor gene. Unphosphorylated form of Rb gene
product inhibits a transcription factor required for DNA replication, while
phosphorylation of Rb allows progression into S-phase.
Difficulty: 2
94. Astrocyte
Ans: Glial cell that provides support for neurons in the brain. Multiple mutations in
astrocytes often result in the generation of cancerous brain tumors referred to as
astrocytomas.
Difficulty: 4
95. Tumor suppressor gene
Ans: Encodes gene products that inhibit unregulated cell division. Mutant tumor
suppressor alleles function recessively in promotion of a cancerous phenotype in a
cell.
Difficulty: 2
96. Growth factor
Ans: Molecule that affects cell proliferation. Generally, growth factors stimulate
proliferation by associating with receptor proteins on the affected cell.
Difficulty: 2
97. Glioblastoma multiforme
Ans: The most malignant form of brain cancer, resulting from multiple mutations in
genes regulating proliferation in a glial cell.
Difficulty: 3
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Experimental Design and Interpretation of Data
98. A patient presents with cancer tumors in several organs. You genotype for several
genes often related to the causation of cancer and find that cells from each disparate
tumor have the same genotype for all of the genes tested. How do you interpret this
data?
Ans: The results are highly suggestive that the cells are clonal, arising from a single
cell, and metastasized to the different organs found to contain cancerous tumors
whose cells are genetically identical for those genes tested.
Difficulty: 4
99. You wish to determine which genes are aberrantly expressed in a certain type of cancer.
How would you measure a possible transcription difference on a genomic level between
the cancer cells and normal cells?
Ans: Isolate tumor cells and normal cells and perform microarray analysis using chips
that contain the entire human genome. Differences in expression are detected by
red/green fluorescence indicating up and down regulation of tumor cells compared
to normal control cells.
Difficulty: 4
100. You have identified a mutation in Gene X that appears along with mutations in three
other genes to cause an increased likelihood for a certain cancer. Develop an assay to
test patients for the polymorphism in Gene X.
Ans: Utilize sequence information to determine differences in restriction enzyme sites
between the wild-type and the mutant alleles. Using an enzyme that cuts one but
not the other you can complete Southern analysis on digested DNA from each and
look for one versus two bands. Alternatively you can design PCR primers and
directly detect the bands by gel electrophoresis.
Difficulty: 4
101. Using yeast, you wish to test the hypothesis that two new temperature-sensitive
mutations you have isolated are involved in different steps of the cell cycle. Describe
the experimental setup necessary to do so.
Ans: Test each single mutant for cell cycle arrests as well as a double mutant (Epistasis
experiment) containing both mutations. The phenotype of the double mutant will
be the same as one of the two single mutants. This will represent the gene
involved in the earlier of the two steps in the cell cycle.
Difficulty: 4
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