Cell Cycle Control and Cell Division Flashcards

1
Q

The entry into mitosis in the cell cycle is triggered by what?

A

M-CDK mediated phosphorylation of specific proteins, along with protein kinases (2 families)

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2
Q

How does G1-CDK activate the E2F proteins?

A

G1-CDK phosphorylates the Rb protein, releasing it from E2F

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3
Q

Which component of the cell-cycle control system detects whether or not the chromosomes are attached to their spindles?

A

APC/C

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4
Q

At what phase of the cell cycle are CDK4-cyclin D and CDK6-cyclin D active?

A

G1 phase

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5
Q

The SMAD proteins target ___ and ___ to prevent cell cycle progression by inhibiting the cyclins.

A

p21; p15

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6
Q

What does the cell cycle involve?

A

DNA replication and cell division to create two identical daughter cells

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7
Q

How is the cell cycle controlled by proteolysis?

A
  • inactive APC/C binds to CDC20 that activates it
  • active APC/C initiates the binding of many ubiquitin molecules to the cyclin-CDK complex
  • ubiquitin tags the cyclin-CDK for proteolysis
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8
Q

___ signaling involves gene regulatory factors and ribosome synthesis to promote protein synthesis and cell growth.

A

m-TOR

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9
Q

The MAPK leads to the activation of what?

A

activation of immediate early gene expression (genes turned on immediately after a mitogen binds to the receptor)

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10
Q

Where is the second checkpoint?

A

at the end of G2, right before the M phase

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11
Q

Is there an intact nuclear envelope still present during prophase?

A

YES

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12
Q

TGF-B works through the ____ proteins.

A

SMAD

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13
Q

____ interact with cell surface receptors on the cell surface, which leads to the activation of a kinase.

A

Mitogens

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14
Q

At what phase is CDK2-cyclin A active?

A

middle of S phase

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15
Q

The ___ cyclin is the protein that binds to S-CDK and moves the cell through the S phase.

A

S

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16
Q

What part of the cyclin-CDK complex gets ubiquinylated?

A

cyclin

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17
Q

The activity of cyclin-CDK is further regulated by Wee1 kinase. What does Wee1 kinase do?

A

Wee1 further phosphorylates cyclin-CDK to render it inactive

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18
Q

What is the pathway of a mitogen-activated protein kinase (MAPK) signaling cascade?

A

stimulus&raquo_space; MAPKKK&raquo_space; MAPKK&raquo_space; MAPK&raquo_space; biological reponse

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19
Q

How does the division of the cytoplasm occur?

A

by contractile rings

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20
Q

What does the loss of CDKs mean after their inactivation?

A

M phase is completed (their targets can be dephosphorylated by various phosphatases present in anaphase)

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21
Q

What CKI helps cells withdraw from the cell cycle when they terminally differentiate?

A

p27

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22
Q

Why does p27 insert itself into the ATP-binding site of the cyclin-CDK complex?

A

to inhibit enzyme activity by preventing it from phosphorylating any targets

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23
Q

What complex initiates the metaphase-anaphase transition?

A

Anaphase-Promoting Complex (APC/C)

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24
Q

What kinase is primarily involved in suppressing CDK1 activity before mitosis by phosphorylating inhibitory sites?

A

Wee1 kinase

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25
Q

The metaphase-to-anaphase transition involves ___.

A

proteolysis

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26
Q

Binding of the CDK to its cyclin leads to what?

A

the movement of the T-loop away from the active site, leading to partial activation

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27
Q

What does M-CDK do to Wee1 kinase in its postive feedback mechanism?

A

inhibits Wee1 kinase; blocks this inhibitory kinase so more of the active form of M-CDK can be made

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28
Q

How many D cyclins are present in mammals?

A

3 (D1, D2, D3)

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29
Q

Each ___ can induce different effects at different times in the cell cycle, based upon the relative presence, absence, or abundance of each specific target.

A

cyclin-CDK

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30
Q

CDK requires the binding of ___ and ___ to become an active enzyme.

A

cyclin; subsequent specific phosphorylation

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31
Q

What are the partners of the G1-CDK complex?

A

cyclin D and CDK4, CDK6

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32
Q

What does the degradation of securin lead to?

A

the activation of a protease that separates the sister chromatids and unleashes anaphase

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33
Q

What tags the cyclin-CDK complex for degradation?

A

binding of many ubiquitin molecules to the cyclin by ubiquitylation enzymes

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34
Q

What are the two critical proteins that initiate the formation of the pre-replicative complex?

A

CDC6 and CDT1

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35
Q

What is CDT1 inhibited by?

A

geminin

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36
Q

What is cancer?

A

inappropriate proliferation

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37
Q

___ can phosphorylate the T-loop at a threonine residue in the T-loop and fully activate the cyclin-CDK complex.

A

CDK-activating kinase (CAK)

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38
Q

The accumulation of the S-CDK concentration initiates the degradation of ____.

A

phosphorylated CDC6

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39
Q

___ activates APC/C and maintains its activity through G1. It is inhibited by CDK activity.

A

CDH1

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40
Q

The activation of ___ triggers the events of mitosis, which includes chromosome segregation.

A

M-CDK

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41
Q

____ starts abruptly with the breakdown of the nuclear envelope. Chromosomes can now attach to spindle microtubules by their kinetochores.

A

Prometaphase

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42
Q

At what phase is CDK2-cyclin E active?

A

end of G1 phase

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43
Q

When does mitosis begin?

A

after the G2/M checkpoint has insured that all of the DNA has been replicated correctly

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44
Q

The ___ cyclin is the protein that moves the cell cycle forward from G1 to S.

A

G1/S

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45
Q

The initiation phase of DNA replication is divided into 2 steps. What are they?

A
  • Late mitosis-early G1

- Onset of S phase

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46
Q

Once E2F proteins are released and activated, it drives the formation and synthesis of ____.

A

C-cyclins and S-CDK

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47
Q

E2F and pRB proteins lead to the compaction of histones to form _____ in the dREAM complex, which renders the cell’s DNA inactive.

A

heterochromatin (because the DNA now cannot be transcribed)

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48
Q

Which complex assesses whether or not the cellular environment is favorable?

A

G1-CDK

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49
Q

In what phase is the pre-replicative complex disassembled?

A

S phase

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50
Q

The ____ stimulate cell division mainly by stimulating G1/S-CDK activity that inhibits intracellular negative controls.

A

mitogens

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51
Q

What are the critical determinants of cancer progression in the cell cycle?

A

genes involved in cell-cycle regulation and control

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52
Q

What is the S phase?

A

where DNA is replicated

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53
Q

When abrupt increase of activity drives entry into mitosis?

A

M-CDK

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54
Q

What is the origin of replication bound by in the phases of the cell cycle where it is inactive?

A

various proteins to block the site

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55
Q

The dREAM complex puts itself into which phase of the cell cycle?

A

G0

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56
Q

What are the partners of the G1/S-CDK complex?

A

cyclin E and CDK2

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57
Q

What is the M phase?

A

where cells divide

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58
Q

___ induces the assembly of the mitotic spindle, chromosome condensation, breakdown of the nuclear envelope, and rearranges the actin cytoskeleton and Golgi.

A

M-CDK

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59
Q

What are the two sister chromatids held together by?

A

kinetochores

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60
Q

What allows for cyclin accumulation to start the next cell cycle?

A

when the G1/S-CDKs are activated in late G1, APC/C is turned off

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61
Q

At each checkpoint, the main cyclin increases in concentration and then decreases as the next phase’s cyclin ___ in concentration.

A

increases

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62
Q

Where is APC/C activated at?

A

in mid-mitosis

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63
Q

___ is thought to promote cell cycle entry by increasing the expression of the genes encoding the G1 cyclins, which results in increased G1-CDK activity.

A

Myc

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64
Q

After the degradation and inhibition of CDC6 and CDT1, the pre-initiation complex arrives and phosphorylates the ____ on the DNA strand so DNA replication can occur.

A

origin proteins

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65
Q

Activation of cyclin-CDK is a prerequisite for many downstream events. A mutation in any of these downstream, tight regulations can lead to ___.

A

cancer

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66
Q

How many major cell cycle checkpoints do eukaryotic cells have?

A

3

67
Q

Where is the metaphase-to-anaphase transition?

A

within the M phase

68
Q

What are the extracellular signals controlling cell division?

A

mitogens
growth factors
survival factors

69
Q

What is the importance of checkpoints in the cell cycle?

A

to make sure the phase in complete before moving on to the next phase

70
Q

What system can arrest the cell cycle whenever a cell fails to complete a process or encounters unfavorable intracellular or extracellular conditions?

A

the cell-cycle control system

71
Q

What kinase is required for the FULL activation of the cyclin-CDK complex?

A

CDK-activating kinase (CAK)

72
Q

What happens during the onset of the S phase of DNA replication?

A

the pre-replication complex nucleates the formation of the pre-initiation complex

73
Q

At what phase of the cell cycle is CDK1-cyclin B active?

A

M phase

74
Q

____ stimulate cell growth by stimulating protein synthesis and inhibiting protein degradation.

A

Growth factors

75
Q

What constituents does a fully active cyclin-CDK contain?

A

CDK
cyclin
activating phosphate

76
Q

What does the F-box domain of the SCF complex do to CKI molecules?

A

initiate the ubiquitylation of CKI to tag it for proteolysis

77
Q

In what phase is APC/C active and CDK is inactive?

A

G1

78
Q

In ____, the replicated chromosomes consisting of two sister chromatids condense. The mitotic spindle begins to assemble between the two centrosomes.

A

prophase

79
Q

What are the three types of control the cell-cycle checkpoint system depends on?

A
  • use of protein kinases (CDKs) for phosphorylation
  • proteolytic events
  • transcriptional regulation
80
Q

What triggers the major events of the cell cycle?

A

the cell-cycle control system

81
Q

___ tend to work through the PIP3 signaling mechanisms.

A

Growth factors

82
Q

Why is EACH cyclin partner important in the cell cycle?

A

because each one determines a different and specific target and then determines which one is subsequently phosphorylated by the CDK subunit

83
Q

In a CDK’s inactive state, the active or catalytic site is blocked by what?

A

the presence of a region called the T-loop

84
Q

During cytokinesis, the re-formation of the ____ array of microtubules nucleated by the centrosome occurs.

A

interphase

85
Q

What general mechanisms determine the movement of cells through the cell cycle?

A
  • concentration
  • phosphorylation state
  • binding partners
86
Q

Do the concentrations of the CDK change?

A

NO - constitutive expression

87
Q

___ has the ability to block rereplication of DNA if it is damaged.

A

M-CDK

88
Q

What are the partners of the M-CDK complex?

A

cyclin B and CDK1

89
Q

Which complex detects DNA damage and halts the cell cycle?

A

G1/S-CDK, S-CDK and M-CDK

90
Q

The cyclin-CDK complexes are also regulated by ___ mechanisms, such as information about DNA damage, step completion, or extracellular environment.

A

inhibitory

91
Q

In ____, the sister chromatids separate to form two daughter chromosomes. Chromosome segregation begins in this phase as microtubules get shorter.

A

Anaphase

92
Q

What triggers the ubiquitylation reaction on the cyclin-CDK to tag it for proteolysis?

A

activation of APC/C by CDC20

93
Q

____ catalyzes the ubiquitylation and degradation of securin and the S- and M-cyclins.

A

APC/C

94
Q

In the absence of cyclin, CDK is ____.

A

in an inactive state

95
Q

What is the G1 phase?

A

resting phase

96
Q

What does the metaphase-to-anaphase checkpoint do?

A

make sure all chromosomes are attached to spindles to trigger anaphase and proceed to cytokinesis

97
Q

What does M-CDK do to CDC25 in its positive feedback mechanism?

A

it stimulates more CDC25 to go from the inactive state to the active state to produce more active M-CDK

98
Q

What is the G2 phase?

A

the phase between the S phase and M phase

99
Q

What only partly activates the cyclin-CDK complex?

A

the movement of the T-loop away from the active site

100
Q

___ suppress programmed cell death and prevent apoptosis.

A

Survival factors

101
Q

How is cyclin gene expression regulated?

A

specific cyclin genes are induced or “turned on” by transcriptional activity

102
Q

What are the partners of the S-CDK complex?

A

cyclin A and CDK2, CDK1

103
Q

What is critical for determining the transitions from one phase to another in the cell cycle?

A

the appearance and disappearance of the various cyclins

104
Q

Where is the first (“start”) checkpoint?

A

at the end of the G1 phase, right before the S phase

105
Q

In ____, the chromosomes align at the equator of the spindle. The kinetochores attach sister chromatids to opposite poles of the spindle.

A

metaphase

106
Q

What molecules assist in the ubiquitylation of CKI (and cyclin)?

A

E1, E2 and ubiquitin

107
Q

___ is inactivated by the binding to the active Rb protein.

A

E2F

108
Q

What partner does a CDK rely on to become an active enzyme?

A

cyclin (= 2 subunit protein)

109
Q

The activation of what enzyme allows the transition of metaphase to anaphase?

A

separase

110
Q

One of the key functions of G1-CDK is to activate the ___ proteins that are themselves regulatory factors.

A

E2F

111
Q

What protein does the cell-cycle checkpoint control system depend on?

A

cyclically activated cyclin-dependent protein kinases (CDKs)

112
Q

What does SCF ubiquinylate?

A

CDK-inhibitor (CKI) proteins in late G1 (ex: p27)

113
Q

p27 is an example of a ___ protein.

A

CDK-inhibitor (CKI)

114
Q

What are the three checkpoints in the eukaryotic cell cycle?

A

Late G1/Start checkpoint
G2/M checkpoint
Metaphase-to-anaphase transition

115
Q

Which phase of the cell cycle is a quiescent or resting phase?

A

G0

116
Q

What does the contractile ring create?

A

a cleavage furrow

117
Q

When the ___ concentration accumulates, it triggers S phase.

A

S-CDK

118
Q

What are the two positive feedback loop mechanisms of M-CDK activity?

A
  • active M-CDK stimulates the activation of CDC25

- active M-CDK inhibits Wee1 kinase

119
Q

What are the first genes that get turned on by the MAPK activation by mitogen binding called?

A

immediate early genes

120
Q

What ubiquitin ligase catalyzes the ubiquitylation of CKI involved in G1 control, such as through the phosphorylation of it?

A

SCF

121
Q

What system ensures the proper timing, order, and fidelity of cellular events?

A

the cell-cycle control system

122
Q

What enzyme can reverse the affects of Wee1 kinase on cyclin-CDK?

A

CDC25 phosphatase

123
Q

When are the inhibitory mechanisms of the cell-cycle control system initiated?

A

when there is damage detected or the environment is unfavorable

124
Q

What complex is bound to CDC6 and CDT1 in the pre-replicative complex?

A

MCM (helicase)

125
Q

___ catalyzes ubiquitylation of regulatory proteins involved at the end of mitosis, such as securin and S- and M-cyclins.

A

APC/C

126
Q

The ___ on active SCF complex recognizes phosphorylated CDK-inhibitor proteins (CKI).

A

F-box

127
Q

The degradation of what leads to inactivation of the CDKs?

A

S- and M-cyclins

128
Q

The cell-cycle control machinery controls ____.

A

cell proliferation

129
Q

Do growth factors directly or indirectly lead to cell growth and cell division?

A

BOTH - can be linear or direct in their mechanisms depending on the protein

130
Q

What is the preferred signaling pathway of EGF?

A

PI3 kinase/Akt signaling

131
Q

During the metaphase-anaphase transition, M-CDK drives the activation of ___.

A

APC/C

132
Q

What specific sites does DNA replication occur at?

A

origins of replication

133
Q

What does EGF eventually promote?

A

cell survival

protein synthesis

134
Q

___ triggers the initial activation of APC/C at the metaphase-anaphase transition.

A

CDC20

135
Q

What type of complex that binds the two sister chromatids in affected in Roberts syndrome?

A

acetyltransferase important for the formation of the cohesion complex

136
Q

The ___ triggers the events that occur in each phase of the cell cycle.

A

cell-cycle control system

137
Q

Can cells enter G0 permanently?

A

YES

138
Q

APC/C activity changes during the cell cycle due to its interactions with ___ and ___.

A

CDC20 (anaphase); CDH1 (late mitosis to G1)

139
Q

What is a key step in the initiation of protein degradation by the proteasome complex?

A

ubiquitylation

140
Q

What cohesion protein is involved in protecting protein linkages that hold the sister chromatids together?

A

securin

141
Q

Myc is an ___.

A

immediate early gene

142
Q

At what phase is CDK1-cyclin A active?

A

end of S phase

143
Q

Which complex detects if there is unreplicated DNA?

A

M-CDK

144
Q

The ___ cyclin begins to increase in concentration from the G2/M checkpoint to reach the metaphase-anaphase transition.

A

M

145
Q

The ____ kinase phosphorylates an activating site in CDKs.

A

CDK-activating (CAK)

146
Q

Does the cell-cycle control system respond to intracellular and extracellular signals?

A

YES

147
Q

___ is stimulated by M-CDK activity.

A

CDC20

148
Q

What does the G2/M checkpoint do?

A

make sure all the DNA has been replicated before proceeding to the M phase for mitosis

149
Q

___ binds to both subunits of the active cyclin-CDK complex, distorting the active site of CDK and inserting itself into the ATP-binding site to inhibit enzyme activity.

A

p27

150
Q

What is the central component of the cell-cycle control system?

A

the series of cyclin-CDK complexes that regulate the transitions through the various phases

151
Q

The concentrations of the three major cyclin proteins oscillate during the cell cycle because their expression is induced to promote the ____ through the cell cycle.

A

transitions

152
Q

What happens during the late mitosis-early G1 phase of DNA replication?

A

the pre-replication complex assembles at the origins of replication

153
Q

Passage through the Start checkpoint of the cell cycle initiates ____ and the S phase of the cell cycle.

A

DNA replication

154
Q

Roberts syndrome results from the decreased ____ and eventual decreased protein synthesis.

A

rDNA transcription

155
Q

In the ___ phase, APC/C complex targets the geminin protein by degrading it and allows the accumulation of CDT1, forming a new pre-replication complex.

A

G2/M

156
Q

Cyclin gene expression is controlled and regulated by ____.

A

transcription

157
Q

At what phase of the cell cycle are heart cells, osteocytes, and neural cells perpetually terminally differentiated at?

A

G0

158
Q

The activation of APC/C leads to the formation of a complex of ___ and ___, which then leads to the degradation of securin.

A

securing; inactive separase

159
Q

What enzyme is primarily involved in controlling CDK1 activation at the onset of mitosis by removing inhibitory phosphates from CDKs?

A

CDC25 phosphatase

160
Q

___ is an ubiquitin ligase similar to APC/C that contains 3 subunits.

A

SCF

161
Q

Why does the entrance into G0 usually occur?

A

due to lack of growth factors or nutrients (or when terminally differentiated)

162
Q

During ____, the two daughter chromosomes arrive at the poles of the spindle and decondense. A new nuclear envelope forms around each set. Division of cytoplasm begins with contraction of contractile ring.

A

telophase

163
Q

Where do cells enter G0 at?

A

from a cell-cycle checkpoint in the G1 phase