19 - 1

19
Regulating the Eukaryotic Cell Cycle

1. During which stage of the cell cycle is the chromosome content of a mammalian liver cell 1n?
a. G1
b. S
c. G2
d none of the above

Ans: d
Question Type: Multiple choice
Chapter 19.1
Blooms: Understanding
Difficulty: Easy

2. What is the difference between a kinetochore and a centromere?

Ans: The kinetochore is a multiprotein complex present at the centromeric region of each sister chromatid. Microtubules from
each spindle pole attach at their respective kinetochore. A centromere is actually part of the chromosome, where two sister
chromatids are physically attached.
Question Type: Essay
Chapter 19.1
Blooms: Applying
Difficulty: Moderate

3. Human genes/proteins that regulate the cell cycle are most easily isolated by:
a. biochemical purification.
b. complementation of Xenopus mutants.
c. complementation of yeast mutants.
d. positional cloning.

Ans: c
Question Type: Multiple choice
Chapter 19.2
Blooms: Applying
Difficulty: Moderate

4. Injection of an immature Xenopus oocyte with MPF induces:

a. meiosis.
b. oocyte maturation.
c. synthesis of progesterone.
d. meiosis and oocyte maturation.

Ans: d
Question Type: Multiple choice
Chapter 19.2
Blooms: Analyzing
Difficulty: Easy
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5. All the following statements about destruction of cyclins are true, except:
a. Destruction is carried out by proteasomes.
b. Destruction is preceded by polyubiquitination.
c. Ubiquitination occurs at specific sites on target molecules.
d. Ubiquitin targets Cdks.

Ans: d
Question Type: Multiple choice
Chapter 19.2
Blooms: Understanding
Difficulty: Moderate

6. Mitotic cyclin levels in early Xenopus embryos are regulated by:

a. phosphorylation.
b. synthesis and degradation of their mRNAs.
c. degradation by APC.
d. degradation by MPF.

Ans: c
Question Type: Multiple choice
Chapter 19.2
Blooms: Understanding
Difficulty: Moderate

7. What is a cdc mutant? What protein is encoded by cdc2 in fission yeast?

Ans: The abbreviation “cdc” stands for “cell-division cycle.” Yeast cdc mutants are typically organisms with a temperature-
sensitive mutation in a gene required for progression through a particular phase of the cell cycle. At the nonpermissive
temperature, cdc mutants arrest at a particular place in the cell cycle. The cdc2 gene encodes the cyclin-dependent kinase (CDK)
protein in the fission yeast Schizosaccharomyces pombe. In addition to encoding CDKs, cdc genes may encode cyclin
subunits or activators of CDKs such as the phosphatase Cdc25.
Question Type: Essay
Chapter 19.2
Blooms: Understanding
Difficulty: Moderate

8. Which of the following is a target of the APC?

a. Cdc25
b. cyclin B
c. separase
d. Cdc28

Ans: b
Question Type: Multiple choice
Chapter 19.3
Blooms: Remembering
Difficulty: Moderate

9. Site-directed mutagenesis of Tyr-15 to Phe in cdc2:

a. results in the wee phenotype.
b. results in a phenotype similar to that caused by mutation in cdc25.
c. increases the possible number of phosphate groups on Cdc2.
d. prevents binding of Cdc13.

Ans: a
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Question Type: Multiple choice

Chapter 19.3
Blooms: Applying
Difficulty: Difficult

10. Which of the following S. pombe mutants is(are) larger than normal?
a. cdc2D
b. cdc25−
c. wee1−
d. cdc25− and wee1−

Ans: b
Question Type: Multiple choice
Chapter 19.3
Blooms: Remembering
Difficulty: Moderate

11. Exit from mitosis depends upon the degradation of:

a. cohesion.
b. condensin.
c. cyclin B.
d. securin.

Ans: c
Question Type: Multiple choice
Chapter 19.3
Blooms: Understanding
Difficulty: Moderate

12. Name three activities of G1 cyclin-CDKs that ensure progression through the cell cycle.

Ans: G1 cyclin-CDKs inactivate the APC, activate expression of S phase cyclins, and phosphorylate the S phase inhibitor, which
targets it for degradation by the SCF.
Question Type: Essay
Chapter 19.3
Blooms: Applying
Difficulty: Moderate

13. Investigators found that the cyclin B concentration rises and falls in synchrony with mitotic events and MPF activity. However,
correlation is not causality. How did they show that cyclin B was responsible for these cell-cycle events?

Ans: To show that cyclin B was responsible for the rise and fall in MPF activity synchronous with mitotic events, investigators
treated Xenopus extracts with RNase, which abolished these events. Upon addition of only cyclin B mRNA, these events resumed.
Question Type: Essay
Chapter 19.3
Blooms: Understanding
Difficulty: Difficult

14. What are the biochemical activities of Wee1 and Cdc25 proteins? How do these activities regulate MPF?

Ans: Wee1 is a kinase that phosphorylates Cdc2 on Tyr-15 and inhibits its activity. Cdc25 is a phosphatase that removes this
phosphate and re-establishes activity in the presence of a phosphate group on Thr-161 in Cdc2.
Question Type: Essay
Chapter 19.3
Blooms: Understanding
Difficulty: Moderate
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15. The S. cerevisiae homolog of Xenopus MPF is:

a. Cdc13-Cdc2.
b. Cdc25-Cdc2.
c. Clb1-Cdc28.
d. Cln3-Cdc28.

Ans: c
Question Type: Multiple choice
Chapter 19.4
Blooms: Remembering
Difficulty: Moderate

16. Which of the following is a substrate of Cln3-Cdc28?

a. SBF
b. SPF
c. MPF
d. MBF

Ans: a
Question Type: Multiple choice
Chapter 19.4
Blooms: Remembering
Difficulty: Moderate

17. Which of the following is targeted by the SCF complex?

a. Cdh1
b. cyclin B
c. securin
d. Sic1

Ans: d
Question Type: Multiple choice
Chapter 19.4
Blooms: Remembering
Difficulty: Moderate

18. During G1, prereplication complexes:

a. are phosphorylated by B-type cyclin-CDKs.
b. are phosphorylated by DDK.
c. bind to ORC.
d. all of the above

Ans: c
Question Type: Multiple choice
Chapter 19.4
Blooms: Understanding
Difficulty: Moderate

19. Cyclin D/Cdk4 functions during:

a. G1.
b. S.
c. G2.
d. M.

Ans: a
Question Type: Multiple choice
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Chapter 19.4
Blooms: Remembering
Difficulty: Easy

20. What is START? How does nutritional status determine whether S. cerevisiae cells will pass START?

Ans: START defines the point in the cell cycle at which yeast cells become irreversibly committed to cell-cycle progression, even
if nutrients are withdrawn. In S. cerevisiae, START occurs late in G1 and regulates entry into S phase. Entry into S phase depends
upon synthesis of the cyclin Cln3. Translation of CLN3 mRNA is regulated by a short upstream open reading frame (ORF) that
inhibits translation of the CLN3 ORF. When nutrients are abundant, there are sufficient translation initiation factors that allow the
CLN3 ORF to be translated.
Question Type: Essay
Chapter 19.4
Blooms: Applying
Difficulty: Moderate

21. What stimulus is required for quiescent cells to re-enter the cell cycle? What events occur after stimulation?

Ans: Quiescent (G0) cells re-enter the cell cycle after stimulation by growth factors. Early response genes are transcribed first;
these include genes encoding transcription factors such as fos and jun. These transcription factors induce expression of delayed-
response genes, including the genes encoding cyclins and CDKs. In particular, expression of cyclin D is required for cyclin D-
CDK4/6 phosphorylation of Rb, which leads to inactivation of Rb as a repressor of E2F. E2F is the transcription factor required for
expression of S phase genes, including the S phase cyclins E and A.
Question Type: Essay
Chapter 19.4
Blooms: Applying
Difficulty: Difficult

22. After addition of serum to G0-arrested mammalian cells, two classes of genes are expressed: early-response genes and delayed-
response genes. Explain why expression of delayed-response genes is blocked by inhibitors of protein synthesis but expression of
early-response genes is not.

Ans: Transcription of early-response genes after addition of growth factors results in mobilization of signal-transduction cascades
that activate preexisting transcription factors in the cytosol or nucleus. Many of the early-response genes encode transcription
factors, such as c-Fos and c-Jun, which stimulate transcription of the delayed-response genes. Thus, activation of delayed response
genes requires protein synthesis.
Question Type: Essay
Chapter 19.4
Blooms: Applying
Difficulty: Moderate

23. Breakdown of the nuclear envelope during mitosis is accomplished by CDK-dependent phosphorylation of lamins:
a. A and C, but not B.
b. A and B, but not C.
c. B and C but not A.
d. A, B, and C.

Ans: d
Question Type: Multiple choice
Chapter 19.5
Blooms: Remembering
Difficulty: Easy

24. The stable attachment of sister kinetochores to microtubules emanating from opposite spindle poles is called:
a. merotelic attachment.
 19 - 6

b. syntelic attachment.
c. amphitelic attachment.
d. monotelic attachment.

Ans: c
Question Type: Multiple choice
Chapter 19.5
Blooms: Understanding
Difficulty: Moderate

25. Describe the experiment that demonstrated that phosphorylation of nuclear lamins is required for nuclear envelope breakdown
during mitosis.

Ans: Site-directed mutagenesis was used to generate nuclear lamin A that could not be phosphorylated by MPF by converting the
serines that are normally phosphorylated to alanines. Expression vectors encoding wild-type or nonphosphorylatable nuclear lamin
A were transfected into mammalian cells in culture. In the cells expressing wild-type lamin A, immunofluorescence revealed that
lamin A was localized to the nuclear membrane during interphase and then diffusely throughout the cytoplasm during mitosis.
Nonphosphorylatable nuclear lamin A remained localized to an intact nuclear envelope, even when cells were in mitosis, as
determined by chromosome condensation.
Question Type: Essay
Chapter 19.5
Blooms: Analyzing
Difficulty: Moderate

26. Separase initiates sister chromatid segregation at anaphase by cleaving:

a. APC.
b. Cdc20.
c. cyclin B.
d. Scc1.

Ans: d
Question Type: Multiple choice
Chapter 19.6
Blooms: Remembering
Difficulty: Easy

27. Describe how Cdc14 triggers the exit from mitosis in the budding yeast, S. cerevisiae.

Ans: Cdc14 is a protein phosphatase, which at anaphase is activated by the mitotic exit network. Once activated, Cdc14
dephosphorylates APC/CCdh1 and Sic1, which promotes mitotic cyclin degradation and mitotic CDK inactivation, respectively.
Question Type: Essay
Chapter 19.6
Blooms: Understanding
Difficulty: Moderate

28. Which of the following inhibit(s) cyclin A/Cdk2 activity?

a. INK4
b. p21CIP
c. Rb
d. INK4 and Rb

Ans: b
Question Type: Multiple choice
Chapter 19.7
Blooms: Remembering
Difficulty: Moderate
 19 - 7

29. Failure of which cell-cycle checkpoint is most likely to result in nondysjunction?

a. chromosome-segregation checkpoint
b. DNA-damage checkpoint
c. unreplicated DNA checkpoint
d. dysreplicated DNA checkpoint

Ans: a
Question Type: Multiple choice
Chapter 19.7
Blooms: Understanding
Difficulty: Moderate

30. Chk1is activated by:

a. ATR.
b. Mad1.
c. p53.
d. Mad1 and p53.

Ans: a
Question Type: Multiple choice
Chapter 19.7
Blooms: Remembering
Difficulty: Easy

31. How does p53 function as a tumor-suppressor protein?

Ans: When p53 becomes stabilized in response to damaged DNA, it arrests the cell cycle at G 1, S, or G2 by inducing the
transcription of p21, a stoichiometric inhibitor of all cyclin-CDK complexes. In some circumstances, p53 will induce the
expression of genes that promote cell death by apoptosis. By either arresting the cell cycle or triggering cell death, p53 prevents
propagation of mutations into the next cell generation. The formation of a tumor depends upon the accumulation of multiple
somatic cell mutations.
Question Type: Essay
Chapter 19.7
Blooms: Applying
Difficulty: Moderate

32. How does the presence of unreplicated DNA prevent entry into mitosis?

Ans: Inter–S phase checkpoint control involves ATR and Chk1. The association of ATR with replication forks is thought to
activate its protein kinase activity. Active ATR phosphorylates and activates the Chk1 kinase. Active Chk1 kinase phosphorylates
and inactivates the Cdc25 phosphatase, which otherwise removes the inhibitory phosphate from mitotic CDKs. This prevents
initiation of mitosis. ATR continues to initiate this protein-kinase cascade until all replication forks complete DNA replication and
disassemble.
Question Type: Essay
Chapter 19.7
Blooms: Applying
Difficulty: Difficult

33. Centromeric Rec8 becomes cleaved during:

a. meiosis I.
b. meiosis II.
c. mitosis.
d. none of the above

Ans: b
Question Type: Multiple choice
 19 - 8

Chapter 19.8
Blooms: Remembering
Difficulty: Moderate

34. How do chromosome movements differ between meiosis I and meiosis II? Is spindle composition the basis for this distinction?

Ans: During meiosis I, synapsed homologous chromosomes are segregated into the two daughter cells. During meiosis II, sister
chromatids are segregated as in a mitotic division. Factors associated with the chromosomes rather than the spindles provide the
basis for this distinction because a meiosis I spindle is capable of segregating meiosis II chromosomes properly, and a meiosis II
spindle will segregate meiosis I chromosomes properly.
Question Type: Essay
Chapter 19.8
Blooms: Applying
Difficulty: Difficult

35. Compare cohesin function during mitosis and meiosis.

Ans: During mitosis, sister chromatids are initially associated with cohesin complexes along the full length of the chromatids.
Cohesin complexes become restricted to the region of the centromere at metaphase. Separase cleaves the Scc1 cohesin subunit,
which allows sister chromatids to separate. In metaphase of meiosis I, crossing over between maternal and paternal chromatids
produces synapsis of homologous parental chromosomes. The chromatids of each replicated chromosome are cross-linked by
cohesin complexes along their entire length. Rec8, a meiosis-specific homolog of Scc1, is cleaved in chromosome arms but not in
the centromere, allowing homologous chromosome pairs to segregate into daughter cells. Centromeric Rec8 is cleaved during
meiosis II, allowing individual chromatids to segregate into daughter cells.
Question Type: Essay
Chapter 19.8
Blooms: Analyzing
Difficulty: Difficult
 19 - 9

New Questions

36. During mitosis, the breakdown of the nuclear envelope depends on the:
a. disassembly following proteasomal degradation of intermediate filaments.
b. disassembly of lamin filaments following phosphorylation by mitotic cyclin/cdk complexes.
c. ubiquitination of mitotic cyclin proteins.
d. lamin filament dephosphorylation by cdc14.

Ans: b
Question Type: Multiple choice
Chapter 19.5
Blooms: Understanding
Difficulty: Moderate

37. Which of the following is NOT a way G1/S cyclin/cdks ensure progression through the cell cycle?
a. inactivate APC via Cdh1 phosphorylation
b. phosphorylate the S phase inhibitor (CKI)
c. activate SCF E3 ligase
d. activate expression of S-phase cyclins

Ans: c
Question Type: Multiple choice
Chapter 19.3
Blooms: Understanding
Difficulty: Moderate

38. DNA replication at each origin occurs only once during the cell cycle because of:
a. specificity of the origin-recognition complex (ORC).
b. S phase Cdk phosphorylating MCM helicase.
c. MCM helicase loading by M phase cyclins.
d. G1 cyclin/cdk activation of E2F.

Ans: b
Question Type: Multiple choice
Chapter 19.4
Blooms: Understanding
Difficulty: Easy

39. Separation of spindle poles during spindle formation and anaphase B most likely depends on which of the following?
a. (+) end-directed microtubule motors at the cell cortex
b. (+) end-directed microtubule motors at the kinetochore
c. (−) end-directed microtubule motors in the microtubule overlap zone
d. (+) end-directed microtubule motors in the microtubule overlap zone

Ans: d
Question Type: Multiple choice
Chapter 19.6
Blooms: Understanding
Difficulty: Moderate

40. Which of the following occurs during anaphase A?

a. The spindle elongates.
b. Kinetochores remain attached to shortening kinetochore microtubules.
c. Chromosomes move to the spindle equator.
d. The spindle poles move closer together.

Ans: b
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Question Type: Multiple choice

Chapter 19.6
Blooms: Understanding
Difficulty: Easy

41. You perform an experiment where you prevent Cdc20 from binding to APC
in a cell line that usually completes the cell cycle in 60 minutes. Your experiment prevents Cdc20 from binding to APC for 120
minutes, and then you fix and stain the DNA, securin, separase and cohesin proteins. Which of the following would NOT be found
in the observed cell?

a. The cell would contain condensed chromosomes aligned at the metaphase plate.
b. Cohesins will be localized around the sister chromatids.
c. Securin would be bound to separase (appear to co-localize).
d. The DNA will be decondensed because the cell is in interphase.

Ans: d
Question Type: Multiple choice
Chapter 19.6
Analysis
Difficulty: Moderate