MOLECULAR BIOLOGY OF THE CELL, SIXTH EDITION

Chapter 17: THE CELL CYCLE

© Garland Science 2015

1. Which of the following simplified diagrams better shows the changes in the
concentrations of three major cyclin–Cdk complexes (G1/S-Cdk, S-Cdk, and M-Cdk) in the cell
in different stages of the cell cycle?

G1 G2

2. Resveratrol is a natural compound found in red grapes (and red wine) and is thought to
have beneficial effects in mammals, such as preventing tumor growth and delaying age-related
diseases. In vitro, resveratrol and its derivatives have been shown to cause cell-cycle arrest in S
phase and induce apoptosis. You have analyzed the DNA content of cultured cells in the
presence and absence of these drugs using fluorescence-activated cell sorting. Compared with
control cells (dashed line), which of the following curves do you think better represents the DNA
content of cells treated with these compounds?
 A B

Number of cells

Number of cells
0 1 2 0 1 2

C D
Number of cells

Number of cells

0 1 2 0 1 2

Relative cellular
DNA content
E
Number of cells

0 1 2
Relative cellular
DNA content

Reference: FACS Data Analysis (Questions 3-4)

You have been studying the effect of loss-of-function mutations in the Cdk inhibitor protein
(CKI) p21. You add the drug fucoxanthin to cell cultures harboring either wild-type or mutant
versions of the p21 gene. Fucoxanthin is known to induce cell-cycle arrest in G1. After a day,
you add the thymidine analog BrdU to the culture media, collect the cells after an hour, treat
them with anti-BrdU antibody and the fluorescent DNA stain DAPI, and finally subject them to
fluorescence-activated cell sorting (FACS). The FACS data can be viewed as a two-dimensional
dot plot composed of thousands of dots, in which each cell is represented by one dot at
coordinates that correspond to the intensities of the DAPI fluorescence signal (X axis) and BrdU
fluorescence signal (Y axis) for that cell. Answer the following question(s) according to the
simplified dot plot below, generated from your experiment.

a b

1 1
BrdU signal intensity

BrdU signal intensity

2 3 2 3

DAPI signal intensity DAPI signal intensity

3. Indicate which boxed region (1, 2, or 3) in the FACS plots corresponds better to each of
the following phases of the cell cycle. Your answer would be a three-digit number composed of
numbers 1 to 3, with each number used once, e.g. 312.
( ) G1 phase
( ) S phase
( ) G2 and M phases

4. Which one of the FACS plots (a or b) would you expect to correspond to the loss-of-
function p21 mutants? Write down a or b as your answer.
5. Sort the following schematic diagrams (A to F) to reflect the order of events in a typical
eukaryotic M phase. An interphase cell in G2 phase is drawn on the left for comparison. Your
answer would be a six-letter string composed of letters A to F only, e.g. BCEADF.

G2 phase A B C D E F

6. Consider two mammalian cells, one in G1 and the other in G0 (stationary) phase. If they
are stimulated to pass the restriction point by the addition of an extracellular proliferation signal,
but the signal is then immediately removed, what would you expect to happen?
A. Both cells will replicate their DNA.
B. Only the G1 cell will replicate its DNA.
C. Only the G0 cell will replicate its DNA.
D. Only the G1 cell will start to replicate its DNA, but will stop halfway through the
replication and will not reach G2.
E. Neither of the cells will replicate their DNA.

7. Which of the time points (A to E) in the following schematic drawing of the mammalian
cell cycle represents the restriction point?
E
D A
C
M

G2
G1

B
Answer: B Difficulty: 1 Section: The Cell-Cycle Control System
Feedback: Under favorable conditions and in the presence of signals to grow and divide, cells in
early G1 (or G0) progress through a commitment point near the end of G1 known as Start (in
yeasts) or the restriction point (in mammalian cells).

8. Indicate whether each of the following descriptions better applies to a Wee1 protein (W)
or a Cdc25 protein (C). Your answer would be a four-letter string composed of letters W and C
only, e.g. WWCW.
( ) It is a protein kinase.
( ) It activates M-Cdk complexes.
( ) It is activated by M-Cdk complexes.
( ) Its loss in fission yeast results in small cell size.

9. Mammalian Cdk inhibitor proteins (CKIs) can be grouped into two families based on
their structural and functional differences. The Cip/Kip family proteins (e.g. p21) have a broad
binding specificity. These proteins bind preferentially to already formed cyclin–Cdk complexes
and thus enhance complex formation. However, they inhibit the kinase activity of most
complexes (e.g. S-Cdks), except in the case of G1-Cdk complexes where no inhibition occurs.
Consequently, Cip/Kip family proteins have an overall positive effect on Cdk4/6 activity due to
their help in bringing the subunits together. In contrast, the inhibitors of the INK4 family (e.g.
p16) bind only to the Cdk subunit of G1-Cdks and prevent binding of both the G1 cyclins and the
Cip/Kip family CKIs. Based solely on these findings, would you expect p16 to activate (A) or
inactivate (I) the S-Cdks in the presence of limited amounts of p21?

10. In the fission yeast Schizosaccharomyces pombe, the proteins Cut1 and Cut2 form a
complex that is catalytically inactive. At the onset of anaphase, Cut2 is polyubiquitylated by a
large E3 complex containing Cut4, Cut9, Cut23, and other proteins, and is subsequently
destroyed. Cut1 then cleaves Rad21, a non-SMC component of a complex that also contains two
SMC proteins, thus allowing sister-chromatid separation. Mutations in the cut genes lead to the
cut phenotype, in which the cell attempts cytokinesis without chromosome segregation. Indicate
which of the following proteins or protein complexes corresponds to or contains the product of
the genes cut1 (A), cut2 (B), cut4 (C), and rad21 (D). Your answer would be a four-letter string
composed of letters A to D only, e.g. DCAB.
( ) Securin
( ) Cohesin
( ) Anaphase-promoting complex
 ( ) Separase

11. The following schematic diagram shows the activation of M-Cdk in mitosis. Indicate
which proteins below correspond to those indicated as A to D in the diagram. Your answer
would be a four-letter string composed of letters A to D only, e.g. BACD.

A
B

( ) Wee1
( ) CAK
( ) Cdc25
( ) M-cyclin

12. Indicate whether each of the following occurs mainly in G1 phase (G), S phase (S), or G2
phase (H) of the cell cycle. Your answer would be a four-letter string composed of letters G, S,
and H only, e.g. HGSS.
( ) DNA helicase activation
( ) DNA helicase deposition on DNA at the replication origins
( ) ORC phosphorylation
( ) Licensing of replication origins

13. Which of the following events occurs in mitotic metaphase?

A. Nuclear envelope breakdown
B. Nuclear envelope reassembly
C. Chromosome attachment to spindle microtubules for the first time
D. Chromosome alignment at the spindle equator
 E. Mitotic spindle assembly

14. Consider two kinesin motor proteins at the mitotic spindle midzone: kinesin-5 is a
tetrameric motor that walks toward the plus end of both microtubules to which it is attached via
its motor domains; kinesin-14, on the other hand, walks toward the minus end of one
microtubule while it is attached to another microtubule via its tail domain. How do these motors
affect the length of the spindle?
A. They both work to shorten the spindle.
B. Kinesin-5 works to shorten the spindle whereas kinesin-14 works to lengthen it.
C. Kinesin-5 works to lengthen the spindle whereas kinesin-14 works to shorten it.
D. They both work to lengthen the spindle.

15. How is centrosome duplication similar to DNA replication?

A. They both use a semiconservative mechanism.
B. They are initiated at around the same time in the cell cycle, near the G1/S transition.
C. They are both controlled in such a way that they replicate once and only once per cell
cycle.
D. They are both separated from their sister copies in mitosis.
E. All of the above.

16. Which of the following is more directly driven by active M-Cdk?

A. Centrosome maturation
B. Centrosome duplication
C. Nuclear envelope reassembly
D. Inactivation of APC/C
E. Cell cleavage

17. Indicate true (T) and false (F) statements below regarding mitosis and the changes that it
brings about compared to interphase. Your answer would be a four-letter string composed of
letters T and F only, e.g. TFTF.
( ) Microtubules become greatly stabilized in mitosis compared to interphase.
( ) The number of γ-tubulin ring complexes in the centrosomes increases greatly during
mitosis compared to interphase.
( ) Chromosomes stabilize mitotic microtubules through activation of Ran monomeric G
protein.
( ) A bipolar spindle can be formed even in the absence of centrosomes.
18. Fill in the blank: “The … is a large structure formed at the centromeric region of each
eukaryotic chromosome. It captures spindle microtubules in mitosis, and therefore serves to
attach the chromosomes to the spindle poles.”

19. Which one of the following chromosomes has formed stable attachment(s) to the spindle
microtubules?

A B C

D E

20. The cell cycle can be arrested in mitosis when a single sister-chromatid pair is mono-
oriented on the mitotic spindle. If at this point a glass microneedle is used to pull the mono-
oriented chromosome toward the pole to which it is not attached, the cell proceeds to anaphase.
This observation confirms that …
A. mono-oriented chromosomes are stable.
B. mechanical tension drives the formation of bi-oriented chromosomes.
C. bi-oriented chromosomes activate the spindle assembly checkpoint.
D. lack of mechanical tension at the kinetochore in at least one chromosome prevents
entry into anaphase.
E. mechanical tension at the kinetochore in at least one chromosome is required for
entry into anaphase.
21. Indicate whether each of the following phosphorylation events typically activates (A) or
inactivates (I) the protein that is being phosphorylated. Your answer would be a four-letter string
composed of letters A and I only, e.g. IIIA.
( ) Phosphorylation of Cdc25 by M-Cdk
( ) Phosphorylation of condensin subunits by M-Cdk
( ) Phosphorylation of kinesin-5 by Aurora-A
( ) Phosphorylation of Ndc80 subunits by Aurora-B

22. In the following schematic drawing of a vertebrate prometaphase chromosome as seen

under a microscope, indicate whether the chromosome is more likely to be closer to pole A or
pole B. Write down A or B as your answer.

Toward pole A Toward pole B

Reference: Chromosome Movement in Anaphase (Questions 23-24)

To study chromosome movement during anaphase in mammals, you have injected fluorescently
labeled tubulin subunits into cells such that microtubules can be seen under a fluorescence
microscope. You then use a relatively strong laser beam to bleach the fluorescent dyes in a
limited area of a metaphase cell, as indicated in the schematic diagram below, and follow the
progression of mitosis under the microscope by time-lapse imaging. You then use the images to
measure the change in distance between various components, and plot the results in the graph
below. Answer the following question(s) based on these results.
 Pole A Chromosomes Pole B

Bleached box

5 Distances:
Distance (µm)

Pole A – pole B
Chromosome – pole B
Bleached box – pole B

0
0 2 4 6
Time after anaphase entry (min)

23. Based on the results from the experiment, which is dominant in this cell: anaphase A or
anaphase B? Write down A or B as your answer.

24. Based on the results from your experiment, which force is dominant in chromosome
movement in this cell: polar ejection force (E), microtubule flux (F), or kinetochore microtubule
plus-end depolymerization (P)? Write down E, F, or P as your answer.

25. Imagine a prometaphase chromosome pair that is attached to one spindle pole. Which of
the following would happen if both arms of the chromosome are severed with a strong laser
beam?
A. All chromosome fragments (the centromere-containing fragment and the arm
fragments) would be pushed away from the pole.
 B. Only the two arm fragments would be pulled toward the pole. The kinetochore-
containing fragment would remain stationary.
C. The kinetochore-containing fragment would be pulled toward the pole. The two arm
fragments would move away from the pole.
D. The kinetochore-containing fragment would move away from the pole, but the two
arm fragments would be pulled toward the pole.
E. All chromosome fragments would be pulled toward the pole.

26. If cells that have started mitosis are treated with nocodazole, a drug that depolymerizes
microtubules, what would you expect to happen? Where would you expect Mad2 protein to be
localized?
A. The cells would arrest in prometaphase; Mad2 would be localized to the spindle
poles.
B. The cells would arrest in telophase; Mad2 would be localized to the spindle poles.
C. The cells would immediately enter anaphase, finish mitosis, and enter G1; Mad2
would be localized to the spindle poles.
D. The cells would arrest in prometaphase; Mad2 would be localized to almost all
kinetochores.
E. The cells would arrest in telophase; Mad2 would be localized to almost all
kinetochores.

27. Treatment of dividing cells with a low dose of the antifungal drug benomyl, which
destabilizes microtubules, slows down correct spindle assembly. But at such doses, the spindle is
eventually formed and the cells survive. However, mutations in some genes confer benomyl
sensitivity: the mutant cells die because they fail to arrest the cell cycle in the presence of
unattached kinetochores and progress through anaphase, with disastrous consequences. Which of
the following would you expect to be a benomyl-sensitive mutant?
A. A loss-of-function mutant in the gene encoding Mad2.
B. A mutation causing the overexpression of Cdc20.
C. A loss-of-function mutation in the gene encoding a kinase that inhibits Cdc20–
APC/C.
D. A loss-of-function mutation in the gene encoding a tubulin subunit.
E. All of the above.

28. Which of the following motor proteins are more directly involved in anaphase B?
A. Kinesin-5 on interpolar microtubules and dynein on kinetochore microtubules
 B. Kinesin-13 on kinetochore microtubules and dynein on astral microtubules
C. Kinesins 4 and 10 on interpolar and astral microtubules and dynein on kinetochore
microtubules
D. Kinesin-5 on interpolar microtubules and kinesins 4 and 10 on interpolar and astral
microtubules
E. Kinesin-5 on interpolar microtubules and dynein on astral microtubules

29. The microtubule-binding protein Patronin binds to the minus ends of microtubules at the
spindle pole and protects them from the effect of catastrophe factors. If Patronin activity is
inhibited by injecting an anti-Patronin antibody into Drosophila melanogaster embryos prior to
cellularization, anaphase B is suppressed and the spindles are significantly shorter. Which of the
forces (1 or 2) in the following schematic diagram do you think is mostly responsible for
anaphase B in this organism at this stage? Does the effect of Patronin inhibition resemble that of
kinesin-5 inhibition (I) or overactivation (O)?

1 1

2 2

A. 1; I
B. 1; O
C. 2; I
D. 2; O

30. Mutant Saccharomyces cerevisiae cells that lack the gene encoding securin can divide
more or less normally by mitosis, without significant chromosome segregation defects. Cells
harboring a nondegradable version of securin, on the other hand, arrest in metaphase as expected,
since they cannot activate separase to enter anaphase. Similarly, cells lacking Cdc20 arrest in
metaphase, since they cannot activate APC/C. Finally, cells lacking both securin and Cdc20
arrest in anaphase: they manage to separate sister chromatids, but do not progress much further.
These results suggest that in wild-type cells, …
A. degradation of securin is necessary to trigger sister-chromatid separation.
B. degradation of securin is sufficient to trigger sister-chromatid separation.
 C. Cdc20–APC/C is NOT necessary for sister-chromatid separation.
D. Cdc20–APC/C is NOT necessary for later events in anaphase.
E. All of the above.

31. Indicate true (T) and false (F) statements below regarding cytokinesis in animal cells.
Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF.
( ) The force for cytokinesis is generated by kinesin motors on microtubule bundles that
form the contractile ring.
( ) As the contractile ring constricts, its thickness increases to keep a constant volume.
( ) The midbody forms from bundles of actin and myosin II.
( ) Local activation of Ran GTPase triggers the assembly and contraction of the
contractile ring.

32. Formin nucleates the growth of parallel actin bundles in the cell. Additionally, myosin
motor activity is positively regulated by phosphorylation. The monomeric G protein RhoA is
important in cytokinesis, because it directly or indirectly …
A. activates formins and inactivates myosin light-chain phosphatase.
B. inactivates formins and activates myosin light-chain kinases.
C. activates formins as well as myosin light-chain phosphatases.
D. inactivates formins as well as myosin light-chain kinases.
E. None of the above.

Reference: Contractile-Ring Positioning (Questions 33-35)

Three models for contractile-ring positioning in animal cells are presented in the schematic
diagrams below. Answer the following question(s) according to these models.

Model 1 Model 2 Model 3

33. In classic experiments carried out in the 1960s and schematized below, an egg of the sand
dollar Echinarachnius parma was made into a torus shape using a glass bead on the end of a
needle, to study the influence of microtubules on cleavage-furrow positioning. The cells were
allowed to undergo two rounds of mitosis. After the second mitosis, an extra furrow (indicated
by a red arrowhead) was observed between the two asters that did not have a spindle between
them. Which of the models (1 to 3) is more consistent with this observation? Write down 1, 2, or
3 as your answer.

34. In experiments on the flattened eggs of the sea urchin Tripneustes gratilla, cytokinesis
was analyzed after placing a small physical barrier (e.g. a glass needle or an oil droplet) between
the spindle and various areas of the cell cortex. Blocks that were located over the equatorial
plane prevented furrow formation in the proximal membrane, whereas blocks located in other
areas did not affect furrowing. Which model (1 to 3) is NOT supported by these results? Write
down 1, 2, or 3 as your answer.
 Flattened egg before Furrow after insertion of a needle
cytokinesis perpendicular to the equatorial plane

Normal furrow Furrow after insertion of a needle

parallel to the equatorial plane

35. In the early embryos of Caenorhabditis elegans, defects in the formation of astral
microtubules increase myosin activity throughout the cell cortex. If the spindle is forced to one
side of the cell, the cortical myosin activity is observed mostly at the opposite side of the cell.
Which model (1, 2, or 3) better predicts these observations? Write down 1, 2, or 3 as your
answer.

36. Indicate true (T) and false (F) statements below regarding cytokinesis in eukaryotic cells.
Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF.
( ) The preprophase band, composed of microtubules and actin filaments, marks the site
of cytokinesis in plant cells.
( ) In some cell types, the site of contractile-ring formation is determined before mitosis.
( ) The early cell plate in dividing plant cells appears after phragmoplast formation.
( ) The membrane required for the newly formed cell plate in plant cells is provided by
endocytosis from the equatorial plasma membrane.
37. In most mammalian cells, low M-cyclin protein levels are maintained during G1 phase.
What is mainly responsible for maintaining these low levels?
A. Cdc20–APC/C
B. Cdh1–APC/C
C. Skp2–SCF
D. β-trCP–SCF
E. p27

38. In the following schematic diagram of an early Drosophila embryo, which step (A to C)
corresponds to cellularization? Write down A, B, or C as your answer.

A B C

Fertilized
egg

39. Indicate whether each of the following, when active, tends to activate (A) or inactivate (I)
M-Cdks. Your answer would be a four-letter string composed of letters A and I only, e.g. IIAI.
( ) M-Cdk
( ) Cdc20–APC/C
( ) Cdh1–APC/C
( ) Sic1

40. How is Cdc20–APC/C similar to Cdh1–APC/C?

A. They are both active throughout interphase.
B. They are both inhibited by M-Cdk.
C. They both inhibit M-Cdk activity.
D. They are both activated suddenly at the onset of mitosis.
E. They are both inactivated soon after anaphase.
41. Which division in meiosis is more similar to mitosis? In which division do sister
chromatids separate from each other?
A. Meiosis I; meiosis I
B. Meiosis I; meiosis II
C. Meiosis II; meiosis I
D. Meiosis II; meiosis II

42. Which stage is usually the longest in meiosis?

A. Prophase I
B. Prometaphase I
C. Telophase I
D. Prophase II
E. Prometaphase II

43. Indicate true (T) and false (F) statements below regarding meiosis in eukaryotic cells.
Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF.
( ) Bivalents form before prophase I.
( ) Crossing-over begins before the synaptonemal complex assembly.
( ) Chiasmata can first be seen under the microscope after the disassembly of the
synaptonemal complexes.
( ) All recombination events lead to crossovers.

44. In the following schematic diagram of a meiotic bivalent in diplotene, indicate whether
each of the following chromatid pairs have undergone DNA exchange (E) or not (N). The
different color of the final form of chromatid 3 is for clarity only. Your answer would be a four-
letter string composed of letters E and N only, e.g. NENE.
 1
2
3
4

( ) Chromatids 1 and 3
( ) Chromatids 1 and 4
( ) Chromatids 2 and 3
( ) Chromatids 2 and 4

45. Loss of the gene encoding shugoshin in many multicellular organisms leads to sterility,
suggesting defects in meiosis. What would you expect to occur in meiotic cells lacking
shugoshin?
A. The homologs fail to separate in anaphase I.
B. The sister chromatids fail to separate in anaphase II.
C. All chromatids separate prematurely in anaphase I.
D. Removal of cohesion between homolog arms fails in prophase I.
E. Removal of cohesion between sister chromatids fails in prophase II.

46. Indicate whether each of the following descriptions better applies to mitogens (M),
growth factors (G), or survival factors (S). Your answer would be a four-letter string composed
of letters M, G, or S only, e.g. GMSG.
( ) They unblock cell-cycle progression
( ) They suppress apoptosis
( ) They trigger a wave of G1/S-Cdk activity
( ) They inhibit the degradation of cellular macromolecules
47. Which one better supports cell proliferation when added to fibroblast cultures: serum or
plasma? This activity is due to the presence of mitogens in this fluid. What is responsible for
making these mitogens?
A. Serum; red blood cells
B. Serum; platelets
C. Plasma; red blood cells
D. Plasma; white blood cells
E. Plasma; platelets

48. Which of the following is an inhibitory extracellular signal for cell proliferation?
A. EGF
B. TGFβ
C. Erythropoietin
D. IGF
E. PDGF

49. Which of the following cell populations in our body has the highest mitotic index?
A. Neurons
B. Hepatocytes
C. Red blood cells
D. Fibroblasts
E. Skeletal myocytes

50. Which of the following proteins is the product of an immediate early gene expressed
following mitogenic stimulation of cell-cycle entry?
A. E2F
B. Rb
C. Myc
D. G1-cyclins
E. All of the above

51. Which of the following events occurs at the onset of S phase in a mitogen-stimulated
vertebrate cell?
A. Activation of Cdh1–APC/C
B. Activation of Rb
C. Activation of geminin
 D. Activation of Cdc20
E. All of the above

52. Which of the following events contributes to driving the mammalian cell past the
restriction point of the cell cycle?
A. Phosphorylation of Cdh1–APC/C by G1/S-Cdk
B. Destruction of CKIs that target S-Cdks
C. Phosphorylation of Rb by G1-Cdk, G1/S-Cdk, and S-Cdk
D. Activation of E2F gene expression by active E2F protein
E. All of the above

53. In the following schematic diagram of a typical eukaryotic cell cycle, choose two major
time points (among A to E) at which the cell-cycle control system normally arrests the cycle if
DNA damage is detected. Your answer would be a two-letter string composed of letters A to E
only in alphabetical order, e.g. CE.

E
D A
C
M

G2
G1

54. A cell has been subjected to ultraviolet irradiation, causing a significant number of
mutations in the genome. Which of the following would you NOT expect to occur as a result?
A. Activation of the protein kinase ATR
B. Activation of the protein kinase Chk1
C. Inactivation of the protein phosphatase Cdc25
D. Binding of p53 to Mdm2
 E. Stabilization of p53

55. In a multicellular organism such as a mammal, loss-of-function mutations in many genes

can contribute to the development of cancer. These genes are therefore called tumor suppressors.
In their absence, the cell fails to stop progression through the cell cycle under conditions in
which normal cells would arrest, paving the way for tumorigenesis. Indicate whether each of the
following proteins is (Y) or is not (N) expected to be the product of a tumor suppressor gene
based on its function in the cell cycle. Your answer would be a four-letter string composed of
letters Y and N only, e.g. YNNN.
( ) Rb
( ) Myc
( ) p53
( ) p21

56. Indicate true (T) and false (F) statements below regarding cellular control of growth and
division. Your answer would be a four-letter string composed of letters T and F only, e.g. TFTF.
( ) Replicative cell senescence usually arises due to the accumulation of mutations in
genes encoding S- and M-cyclins.
( ) Replicative cell senescence is caused by the induction of apoptosis by p53.
( ) Excessive mitogenic stimulation can result in Mdm2 activation and the induction of
apoptosis or cell-cycle arrest.
( ) The Mdm2 inhibitor Arf induces cell-cycle progression.

57. You have synchronized a culture of HeLa cells so that the cells are all at the same stage
in the cell cycle. You then treat the cells with serum containing nutrients and growth factors in
the presence or absence of the drug rapamycin. The distribution of cell sizes in the two cell
populations is shown below. Based on these results, do you think rapamycin is an activator or
inhibitor of the TOR complex? Is the S6 kinase expected to be up-regulated or down-regulated in
the presence of rapamycin?
 Before serum addition
5 hours after serum addition with rapamycin
5 hours after serum addition without rapamycin

Cell number

Cell size

A. Activator; up-regulated
B. Activator; down-regulated
C. Inhibitor; up-regulated
D. Inhibitor; down-regulated
Answers
1. Answer: A
Difficulty: 2
Section: The Cell-Cycle Control System
Feedback: The G1/S-Cdk activity (solid black curve) peaks in late G1 and falls in S phase.
The S-Cdk levels (solid gray curve) remain elevated through S and G2 until early M
phase. M-Cdk (dashed gray curve) accumulates before entry into mitosis, but their level
falls in mid-mitosis.
2. Answer: B
Difficulty: 3
Section: The Cell-Cycle Control System
Feedback: S-phase arrest will increase the proportion of cells in this phase; that is, cells
with a relative cellular DNA content of between 1 and 2.
3. Answer: 213
Difficulty: 3
Section: The Cell-Cycle Control System
Feedback: After a short incubation with BrdU, cells that are replicating their DNA (in S
phase) would incorporate the compound and would show a high BrdU signal compared to
cells that are in G1, G2, or M phases. The DAPI signal intensity represents the total DNA
content, which increases from G1 to S to G2 phases.
4. Answer: a
Difficulty: 3
Section: The Cell-Cycle Control System
Feedback: Given the significant difference between the results from wild-type and p21
mutant cells, fucoxanthin appears to arrest the cell cycle (in G1) by activating a p21-
dependent pathway. Loss of p21 (plot a) therefore blocks the cell-cycle arrest induced by
the drug.
5. Answer: CFEDAB
Difficulty: 2
Section: Overview of the Cell Cycle
Feedback: The M phase includes mitotic prophase (C), prometaphase (F), metaphase (E),
anaphase (D), telophase (A), and finally cytokinesis (leading to B).
6. Answer: A
Difficulty: 1
Section: Overview of the Cell Cycle
Feedback: Once a cell passes the restriction point, it is committed to DNA replication
(and cell division) even if the stimulating signals are removed.
7. Answer: B
Difficulty: 1
Section: The Cell-Cycle Control System
Feedback: Under favorable conditions and in the presence of signals to grow and divide,
cells in early G1 (or G0) progress through a commitment point near the end of G1 known
as Start (in yeasts) or the restriction point (in mammalian cells).
8. Answer: WCCW
Difficulty: 2
 Section: The Cell-Cycle Control System
Feedback: Wee1 kinases phosphorylate and inactivate cyclin–Cdk complexes; Cdc25
phosphatases do the opposite. In a positive feedback loop at the onset of mitosis, M-Cdk
inactivates its inactivator, Wee1, and activates its activator, a Cdc25. The small cell size
in wee mutants can result from Wee1 depletion.
9. Answer: I
Difficulty: 3
Section: The Cell-Cycle Control System
Feedback: In the absence of p16, p21 is sequestered by the G1-Cdk complex. Active p16,
however, prevents p21 from binding, making it available to inhibit the S-Cdk complexes.
10. Answer: BDCA
Difficulty: 2
Section: S Phase
Feedback: Rad21 is a Scc1 homolog, which is cleaved by separase in the metaphase–
anaphase transition.
11. Answer: CBDA
Difficulty: 2
Section: Mitosis
Feedback: Activation of M-Cdk is sharpened by positive feedback loops in which M-Cdk
activates its activator (Cdc25) and inactivates its inactivator (Wee1) by phosphorylation.
12. Answer: SGSG
Difficulty: 2
Section: S Phase
Feedback: The loading of inactive DNA helicases onto the replication origins and the
formation of the prereplicative complex (preRC) occur in late mitosis and early G1. In S
phase, the helicases are activated to initiate DNA replication, while the origin is
prevented from refiring by origin recognition complex (ORC) phosphorylation and other
mechanisms.
13. Answer: D
Difficulty: 1
Section: Mitosis
Feedback: The alignment of chromosomes at the cell equator is the hallmark of
metaphase.
14. Answer: C
Difficulty: 2
Section: Mitosis
Feedback: While kinesin-5 pushes the two poles of the spindle apart by walking toward
the plus end of antiparallel microtubules, kinesin-14 pulls the two poles toward each
other by walking toward the minus end of interpolar microtubules in the midzone.
15. Answer: E
Difficulty: 1
Section: Mitosis
Feedback: The centrosomes, like the chromosomes, are duplicated only once during each
cell cycle. Centrosome duplication is triggered by the activation of G1/S-Cdk. Both
 centrosome duplication and DNA replication employ a semiconservative mechanism. The
two new centrosomes remain together on one side of the cell until entry into mitosis.
16. Answer: A
Difficulty: 1
Section: Mitosis
Feedback: The M-Cdk is responsible for most events in early mitosis, including spindle
assembly and centrosome maturation. It is inactivated later in mitosis, resulting in the
events of telophase and cytokinesis.
17. Answer: FTTT
Difficulty: 2
Section: Mitosis
Feedback: Mitosis is accompanied by a dramatic reorganization of the microtubule
cytoskeleton, with a significant increase in microtubule instability. At the same time,
centrosome maturation greatly increases microtubule nucleation. The capture of
microtubules by chromosomes stabilizes microtubules in part by activating Ran, a
monomeric GTPase. The ability of mitotic chromosomes to stabilize and organize
microtubules makes it possible to form bipolar spindles even in the absence of
centrosomes.
18. Answer: kinetochore
Difficulty: 1
Section: Mitosis
Feedback: Kinetochores are giant protein structures that attach sister chromatids to the
mitotic spindle.
19. Answer: C
Difficulty: 1
Section: Mitosis
Feedback: Bi-oriented chromosomes are stabilized due to the unique tension created.
20. Answer: D
Difficulty: 2
Section: Mitosis
Feedback: This important experiment confirms the importance of mechanical tension
within the kinetochores in the spindle assembly checkpoint mechanism.
21. Answer: AAAI
Difficulty: 2
Section: Mitosis
Feedback: M-Cdk activates the Cdc25 phosphatase in a positive feedback loop. It also
phosphorylates condensin subunits, stimulating DNA binding and supercoiling activity.
Along with Aurora-A, it also phosphorylates kinesins such as kinesin-5, stimulating
microtubule binding and motor activity. Without tension in the kinetochore, Aurora-B
phosphorylates and inactivates components of Ndc80, lowering its affinity for
microtubule plus ends.
22. Answer: A
Difficulty: 2
Section: Mitosis
 Feedback: The polar wind, mediated by plus-end directed kinesin motors, gets stronger as
the chromosome approaches a pole, and pushes the chromosome arms toward the
opposite pole.
23. Answer: A
Difficulty: 2
Feedback: In this example, the two poles are pushed away from each other only slightly
during anaphase.
24. Answer: F
Difficulty: 3
Feedback: In these cells, the chromosomes seem to approach the nearby pole as fast as
the bleached zone approaches the pole, meaning that the microtubule subunit flux is
enough to explain the poleward chromosome movement.
25. Answer: C
Difficulty: 2
Section: Mitosis
Feedback: The result of such an experiment has provided evidence for polar ejection
forces acting on chromosome arms.
26. Answer: D
Difficulty: 2
Section: Mitosis
Feedback: A cell treated with nocodazole fails to assemble a functional spindle, and
therefore arrests in prometaphase with the chromosomes left unattached. Mad2 is
recruited to unattached kinetochores and activates the spindle assembly checkpoint,
preventing the onset of anaphase.
27. Answer: E
Difficulty: 3
Section: Mitosis
Feedback: All of these mutations make the cells more sensitive to the benzimidazole
drug.
28. Answer: E
Difficulty: 1
Section: Mitosis
Feedback: Two major forces act in anaphase B. Kinesin-5 pushes the two poles away
from each other, and dynein pulls the poles toward the cell periphery.
29. Answer: A
Difficulty: 3
Section: Mitosis
Feedback: The force generated by kinesin-5 to lengthen the spindle in anaphase B is
counteracted by catastrophe factors at the poles, which are inhibited by Patronin.
Inhibition of Patronin would therefore result in anaphase B suppression.
30. Answer: A
Difficulty: 3
Section: Mitosis
Feedback: Both Cdc20 activation and securin destruction are necessary for sister-
chromatid separation because cells in which either of these fail to occur are observed to
 arrest in metaphase. Securin degradation does not appear to be sufficient for sister-
chromatid separation, as the cells lacking securin are more or less healthy, meaning other
mechanisms also control the separation. Cdc20 appears to be necessary for anaphase
beyond sister-chromatid separation, since the double knockouts still arrest in anaphase
despite lacking securin.
31. Answer: FFFF
Difficulty: 1
Section: Cytokinesis
Feedback: The contractile ring is based on actin and myosin II, constricts in a dynamic
fashion, and gradually disassembles. RhoA GTPase helps assemble this structure.
32. Answer: A
Difficulty: 1
Section: Cytokinesis
Feedback: This G protein activates formin as well as multiple protein kinases, including
the Rho-activated kinase Rock. Rock phosphorylates regulatory myosin light chains and
also inhibits myosin light-chain phosphatase by phosphorylation.
33. Answer: 1
Difficulty: 2
Section: Cytokinesis
Feedback: The astral stimulation model (1) predicts this outcome. The central spindle
stimulation model (2) predicts the formation of two furrows when there are two spindles.
However, it is also likely that a midzone-like structure formed between the two spindles
in these experiments, and so model 2 could also be correct here. The astral relaxation
model (3) predicts the formation of two furrows in the first division.
34. Answer: 3
Difficulty: 2
Section: Cytokinesis
Feedback: The astral relaxation model (3) cannot explain these results.
35. Answer: 3
Difficulty: 2
Section: Cytokinesis
Feedback: These observations are in better agreement with the astral relaxation model
(3).
36. Answer: TTTF
Difficulty: 2
Section: Mitosis
Feedback: In plant cells, the preprophase band assembles just before mitosis and marks
the site of cytokinesis. The assembly of the cell plate between the two daughter cells is
then guided by phragmoplast. The membrane required for the formation of cell plate
comes from the Golgi apparatus.
37. Answer: B
Difficulty: 1
Section: Mitosis
Feedback: Cdh1–APC/C activity increases in late mitosis and keeps the M-Cdk activity
low via M-cyclin degradation during G1.
38. Answer: C
Difficulty: 1
Section: Cytokinesis
Feedback: Cellularization is the coordinated cytokinesis that occurs after 13 mitoses in
early fruit-fly development.
39. Answer: AIII
Difficulty: 2
Section: Mitosis
Feedback: Both Cdc20–APC/C and Cdh1–APC/C target M-cyclins for degradation. M-
Cdk, in turn, activates the former and inactivates the latter. Sic1 in budding yeast is an
example of a CKI that also inhibits M-Cdks. M-Cdk activates the expression of M-cyclin
genes in a positive feedback loop, although its activity is also regulated by negative
feedback, for example through Cdc20–APC/C mentioned above.
40. Answer: C
Difficulty: 2
Section: Mitosis
Feedback: Although regulated differently, both APC/C complexes target M-cyclins for
degradation.
41. Answer: D
Difficulty: 2
Section: Meiosis
Feedback: Meiosis II resembles mitosis, in which sister chromatids segregate during
anaphase.
42. Answer: A
Difficulty: 1
Section: Meiosis
Feedback: Prophase I is by far the longest stage in meiosis.
43. Answer: FTTF
Difficulty: 2
Section: Meiosis
Feedback: Bivalents form and recombination begins during leptotene in prophase I. The
synaptonemal complex is formed during zygotene and pachytene, and disassembled in
diplotene, which is when chiasmata become visible. Only some recombination events
lead to crossovers; that is, reciprocal exchange of DNA.
44. Answer: NNEN
Difficulty: 2
Section: Meiosis
Feedback: There are two chiasmata in this drawing, both corresponding to exchange
between chromatids 2 and 3.
45. Answer: C
Difficulty: 1
Section: Meiosis
Feedback: In the absence of shugoshin, cohesin complexes at the centromeric regions are
no longer protected from phosphorylation. The phosphorylated cohesin subunits are then
 cleaved by separase in anaphase I. Consequently, the sister chromatids segregate
randomly in anaphase II.
46. Answer: MSMG
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: Mitogens stimulate cell division by promoting cell cycle progression. Survival
factors promote cell survival by suppressing apoptosis. Growth factors stimulate increase
in cell mass by promoting anabolic metabolism.
47. Answer: B
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: When blood clots, the incorporated platelets release the contents of their
secretory vesicles, containing platelet-derived growth factor (PDGF) among other
proteins.
48. Answer: B
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: Transforming growth factor-β (TGFβ) and its relatives are amongst the best-
understood inhibitory signal proteins.
49. Answer: D
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: Since they spend less time than the other cells in G1, fibroblasts have a high
mitotic index. Note that not all cells with a rapid turnover have a high mitotic index.
50. Answer: C
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: Once produced, Myc activates the transcription of delayed-response genes
such as G1-cyclins. These in turn activate transcription regulators of the E2F family.
51. Answer: C
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: Once the activity of Cdh1–APC/C falls in late G1, geminin starts to
accumulate.
52. Answer: E
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: All of these processes ensure a sharp transition from G1 to S phase, as well as
sustained S-Cdk activity afterward.
53. Answer: BC
Difficulty: 1
Section: Control of Cell Division and Cell Growth
Feedback: These two transitions are the major time points at which DNA damage is
detected and cell-cycle arrest occurs, although the cell can sense DNA damage and arrest
the cell cycle at other points throughout the cycle, including in S phase.
54. Answer: D
Difficulty: 2
Section: Control of Cell Division and Cell Growth
Feedback: Activation of the DNA damage response involves the two upstream kinases
ATM and ATR, which phosphorylate and activate the Chk1 and Chk2 kinases. Cdc25
phosphatases can be inhibited by phosphorylation in this pathway, whereas p53
phosphorylation stabilizes the protein by reducing its interaction with its inhibitor Mdm2.
55. Answer: YNYY
Difficulty: 2
Section: Control of Cell Division and Cell Growth
Feedback: Loss-of-function mutations in p53, Rb, and p21 are found in human cancers.
Myc, on the other hand, has the opposite effect: gain-of-function mutations in Myc can
drive cancer.
56. Answer: FFFF
Difficulty: 2
Section: Control of Cell Division and Cell Growth
Feedback: Replicative cell senescence is a result of the shortening of telomeres in
somatic cells that lack telomerase activity. Eventually, the unprotected chromosome ends
trigger cell-cycle arrest or apoptosis through p53 activation. Excessive stimulation by
mitogens can also activate p53, since the cell-cycle inhibitor Arf is activated under
excessive Myc or Ras activity and inhibits the p53 inhibitor Mdm2.
57. Answer: D
Difficulty: 3
Section: Control of Cell Division and Cell Growth
Feedback: Rapamycin inhibits the mammalian TOR complex that is activated in response
to growth factors in a PI 3-kinase-dependent manner. As a result, cell growth is retarded
in a number of ways, including by inhibition of TOR-mediated activation of S6 kinase.