ch.18 Flashcards

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1
Q

Each parental cell gives rise to two _______ cells on completion of a cycle of cell division.

A

daughter

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2
Q

Eukaryotic cells progression through the cell cycle is controlled by what?

A

protein kinases

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3
Q

Defects in cell cycle regulations is a common cause of what?

A

the abnormal proliferation of cancer cells

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4
Q

The division cycle of most cells consists of 4 coordinated processes, what are they?

A
  1. cell growth
  2. DNA replication
  3. distribution of the duplicated chromosomes to daughter cells
  4. cell division
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5
Q

In prokaryotes, chromosomes is ______ and the daughter DNA is separated into the two daughter cells.

A

duplicated

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6
Q

What are the 4 cell cycle phases in eukaryotes?

A

M, G1, S, and G2

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7
Q

What is the M phase?

A

mitosis (nuclear division)

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8
Q

The M phase usually ends with what?

A

cell division (cytokinesis)

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9
Q

What is Interphase?

A

period between mitoses

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10
Q

What is interphase divided into?

A

G1, S, and G2

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11
Q

What is G1 phase?

A
  • Interval between mitosis and DNA replication
  • The cell is metabolically active and growing
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12
Q

What happens in S phase?

A

DNA replication

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13
Q

What happens in G2 phase?

A
  • cell growth continues
  • proteins are synthesized in preparation for mitosis
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14
Q

Early embryos may have cell cycles of ____ minutes

A

30

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15
Q

In early embryos, there is no what?

A

no growth (G1 or G2) phase

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16
Q

Animal cells in ____ are diploid.

A

G1

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17
Q

diploid = _____ DNA content

A

2n

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18
Q

In S phase, replication increases the DNA content to ____

A

4n

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19
Q

How can DNA content be determined?

A

by incubation of cells with a fluorescent dye that binds to DNA

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20
Q

What is fluorescence intensity of individual cells measured in?

A

a flow cytometer or fluorescence-activated cell sorter

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21
Q

The progression of cell division is regulated by what?

A

extracellular and internal signals

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22
Q

What are the control points that regulate cellular processes?

A

growth, DNA replication, mitosis

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23
Q

What is a major control point?

A

START

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24
Q

what does START control?

A

controls progression from G1 to S

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25
Q

What happens once cells pass START?

A

committed to entering S phase and undergoing one division cycle

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26
Q

What is passage through START highly regulated by?

A

external signals, such as nutrient availability and cell size

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27
Q

What happens if there is a shortage of nutrients?

A

yeast cells can arrest the cycle at START and enter a resting phase

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28
Q

Yeast cells must reach a minimum ____ to pass START.

A

size

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29
Q

Small daughter cells of budding yeasts spend a longer time in ___ and grow more than the large mother cell.

A

G1

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30
Q

Passing through the restriction point commits the cell to what phases?

A

S and M phase

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31
Q

If appropriate growth factors are not present in G1, what happens?

A

Progression stops at the restriction point and cells enter G0

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32
Q

What is G0?

A

a resting stage

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33
Q

Skin fibroblasts are arrested in G0 until stimulated by what?

A

platelet-derived growth factor to proliferate and repair wound damage

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34
Q

What is the cell cycle that’s controlled by transition from G2 to M, the point at which cell size and nutrient availability are monitored?

A

the fission yeast schizosaccharomyces pombe cell cycle

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35
Q

Cell cycle control in G2 also occurs in animal _____

A

oocytes

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36
Q

How long do vertebrate oocytes remain arrested in G2 for?

A

long periods (decades in humans)

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37
Q

In vertebrate oocytes, progression to M phase is triggered by what?

A

hormonal stimulation

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38
Q

Coordination of the cell cycle phases is dependent on a series of cell cycle _____

A

checkpoints

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39
Q

What do cell cycle checkpoints do?

A

prevent entry into the next phase until events of the preceding phase have been completed

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40
Q

DNA damage checkpoints ensures what?

A
  • that damaged DNA is not replicated and passed on to daughter cells
  • cell cycle is arrested until DNA is repaired or replicated
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41
Q

What does the spindle assembly checkpoint do?

A

stops mitosis at metaphase if chromosomes are not properly aligned on the spindle

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42
Q

What triggers the major eukaryotic cell cycle transitions?

A

a conserved set of protein kinases

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43
Q

The studies of frog oocytes contributed to identification of what?

A

frog oocytes are arrested in G2 until hormonal stimulation triggers entry into M phase

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44
Q

What was cytoplasmic factor was responsible for the study of frog oocytes discovery?

A

maturation promoting factor (MPF)

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45
Q

MPF is also present in what?

A

somatic cells

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46
Q

MPF incudes what?

A

entry into M phase

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47
Q

MPF appeared to act as what?

A

a general regulator of the transition from G2 to M

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48
Q

The genetic analyses of yeast determined what?

A

temperature-sensitive mutants that were defective in cell cycle progression

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49
Q

cell division cycle mutants (cdc) genes are required for what?

A

passage through START and entry into mitosis

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50
Q

What do cell division mutants (cdc) do?

A

encode protein kinases

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51
Q

what is Cdk1?

A

the protein kinase that is a cell cycle regulator conserved in all eukaryotes

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52
Q

Protein synthesis in early sea urchin embryos discovered what?

A

two proteins (cyclins) that accumulate throughout interphase but rapidly degrade at the end of mitosis

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53
Q

When the 3 experimental approaches to cell cycle regulators converged, how were the components determined to function together?

A
  • MPF was composed of Cdk1 and cyclin B
  • cyclin B is a regulatory subunit required for catalytic activity of the Cdk1 protein kinase
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54
Q

Research has established that _____ and _____ are members of protein families.

A

Cdk1 and cyclin B

55
Q

In yeasts, what does Cdk1 control?

A

G2 to M transition in association with mitotic B-type cyclins

56
Q

Cdk1 controls passage through START and entry into mitosis in association with what?

A

G1 cyclins or Cln’s

57
Q

What does Cdk stand for?

A

cyclin-dependent kinases

58
Q

Studies of Cdk’s and cyclins in genetically modified mice reveal high level of what?

A

plasticity

59
Q

What does the high level of plasticity of Cdk’s and cyclins allow them to do?

A

compensate for the loss of either Cdk’s or cyclins

60
Q

_____ is capable of substituting for all the other CDk’s

A

Cdk1

61
Q

What are the 2 families of Cdk inhibitors in mammalian cells?

A

Ink4 and Cip/Kip

62
Q

what are one link between growth factor signaling and cell cycle progression?

A

D-type cyclins

63
Q

Growth factors stimulate cyclin D synthesis through what pathway?

A

the Ras/Raf/MEK/ERK pathway

64
Q

Cyclin D1 is synthesized as longa as ____ ______ are present.

A

growth factors

65
Q

Cyclin D1 is rapidly degraded due to what?

A

APC/C ubiquitin ligase

66
Q

As long as growth factors are present through ____, Cdk4, 6/cyclin D complexes drive cells through the restriction point.

A

G1

67
Q

Defects in cyclin D regulation could contribute to what?

A

the loss of growth regulation characteristic of cancer cells

68
Q

Many human cancers arise as a result of defects in what?

A

cell cycle regulation

69
Q

What is Rb?

A

a substrate protein of Cdk4, 6/cyclin D complexes

70
Q

What substrate protein is frequently mutated in many human tumors?

A

Rb

71
Q

What was Rb first identified in?

A

retinoblastoma

72
Q

Rb is the prototype _____ _____ gene

A

tumor suppressor

73
Q

The inactivation of Rb leads to what?

A

tumor development

74
Q

Proteins encoded by tumor suppressor genes act as what?

A

brakes that slow down cell cycle progression

75
Q

In G0 or early G1 \, Rb binds to what?

A

E2F transcription factors

76
Q

When Rb binds to E2F, what does it do?

A

suppresses expression of genes involved in cell cycle progression

77
Q

Progression through the restriction point is mediated by the activation of what?

A

Cdk2/cyclin E complexes

78
Q

In G0 and early G1, Cdk2/cyclin E is inhibited by what?

A

p27 (Cip/Kip family)

79
Q

How is the inhibition of Cdk2 relieved?

A

by multiple mechanisms as cells progress through G1

80
Q

What reduces transcription and translation of p27?

A

growth factor signaling via Ras/Raf/MEK/ERk and PI 3-kinase/Akt pathways

81
Q

When Cdk2 becomes activated, it phosphorylates ____ and targets it for ubiquitylation.

A

p27

82
Q

What is inhibited by Cdk2?

A

APC/C ubiquitin ligase

83
Q

When are high levels of cyclins maintained through S and G2?

A

when APC/C ubiquitin ligase is inhibited by Cdk2

84
Q

what initiates S phase by activating DNA synthesis at replication origins?

A

Cdk2/cyclin E

85
Q

MCM helicase and origin recognition complex (ORC) proteins bind to what during G1?

A

replication origins

86
Q

Cdk2/cyclin E activates the _____ by phosphorylating activating proteins.

A

ORC

87
Q

What does the inhibition of APC/C (by Cdk2/CycE) lead to?

A

the activation of protein kinase DDK

88
Q

What does the protein kinase DDK phosphorylate directly?

A

MCM proteins

89
Q

What does the high activity of Cdk’s during S, G2, and M phases prevent?

A

MCM proteins from reassociating with replication origins

90
Q

Pre-replication complexes can only reform when?

A

during G1 when Cdk activity is low

91
Q

Cell cycle arrest at DNA damage checkpoints is mediated by what?

A

protein kinases ATM and ATR

92
Q

ATM and ATR activate a signaling pathway that leas to what?

A

cell cycle arrest, DNA repair, and programmed cell death

93
Q

What phosphorylates and inhibits Cdc25 phosphatases?

A

Chk1 and Chk2

94
Q

What are requires to activate Cdk1 and Cdk2?

A

Cdc25 phosphatases

95
Q

Inhibition of Cdk2 results in what?

A

cell cycle arrest in G1 and S

96
Q

What does inhibition of Cdk1 result in?

A

arrest in G2

97
Q

In mammalian cells, arrest is also mediated by what protein?

A

p53

98
Q

p53 is phosphorylated by what?

A

ATM and Chk2

99
Q

Increased levels of p53 leads to what?

A

induction of Cdk inhibitor p21

100
Q

what does p21 inhibit?

A

Cdk2/cyclin E or A complexes

101
Q

When Cdk2/cyclin E or A complexes are inhibited, what does that lead to?

A

cell cycle arrest

102
Q

what gene is frequently mutated in about 50% human cancer?

A

p53

103
Q

Around 100% of cancers involve a defect in the ____ pathway.

A

p53

104
Q

loss of ____ prevents cell cycle arrest in response to DNA damage, so the damaged DNA is replicated and passed on to daughter cells.

A

p53

105
Q

What happens in chromatin condensation?

A

phosphorylation of condensins and cohesins

106
Q

what happens in nuclear envelope breakdown?

A

phosphorylation of lamins, nuclear pore complexes, and inner nuclear membrane proteins

107
Q

what happens in fragmentation of golgi apparatus?

A

phosphorylation of golgi matrix proteins

108
Q

What happens in spindle formation?

A

phosphorylation of centrosome, kinetochore, and microtubule-associated proteins

109
Q

Golgi breakdown is mediated by phosphorylation of proteins by _____ and _____ kinases.

A

Cdk1 and Polo-like

110
Q

Reorganization of the cytoskeleton and formation of the mitotic spindle results from what?

A

the dynamic instability of microtubules

111
Q

What are centrosome maturation and spindle assembly are driven by?

A

Aurora and Polo-like kinases at the centrosomes

112
Q

In M phase, microtubule turnover rate ______, resulting in depolymerization and shrinkage of the interphase microtubules.

A

increases

113
Q

In M phase, the number of microtubules radiating from the centrosomes ________.

A

increases

114
Q

In the M phase, the breakdown of the nuclear envelope allows spindle microtubules to what?

A

attach to chromosomes at the kinetochores

115
Q

In M phase, chromosomes in prometaphase do what due to activity of microtubule motors at the kinetochore and centrosomes.

A

shuffle back and forth

116
Q

In the M phase, the balance of forces acting on the chromosomes leads to what?

A

their alignment on the metaphase plate

117
Q

What does the spindle consist of?

A

kinetochore, polar microtubules, astral microtubules, and chromosomal microtubules

118
Q

At the spindle assembly checkpoint, progression to anaphase is mediated by activation of ________

A

APC/C ubiquitin ligase

119
Q

The presence of even one unaligned chromosome is sufficient to prevent what?

A

activation of the APC/C

120
Q

Unattached kinetochores leads to the assembly of the ________ _______ _______.

A

mitotic checkpoint complex (MCC)

121
Q

In the M phase, once all chromosomes are aligned on the spindle, the inhibitory complex is no longer formed and APC/C is ______

A

activated

122
Q

APC/C ________ cyclin B and securin.

A

ubiquitylates

123
Q

Cyclin B and securin inactivates what?

A

Cdk1 and separase

124
Q

What breaks the link between sister chromatids, allowing them to segregate and move to opposite spindle poles?

A

separase degrades cohesin

125
Q

Separation of chromosomes during anaphase proceeds by the action of what?

A

motor proteins associated with the spindle microtubules

126
Q

APC/C also triggers degradation of Aurora and Polo-like kinases, allowing the cell do what?

A

to exit mitosis and return to interphase

127
Q

What triggers cytokinesis?

A

inactivation of Cdk1

128
Q

Cytokinesis of yeast and animal cells is mediated by a _____ _____ of actin and myosin II filaments that forms beneath the plasma membrane

A

contractile ring

129
Q

Ring formation is activated by ______ and _______ kinases.

A

Aurora and Polo-like

130
Q

What pulls the plasma membrane inward?

A

Contraction of the actin-myosin filaments, eventually pinching the cell in half

131
Q

In plant cells, how does cytokinesis proceed?

A

by formation of new cell walls and plasma membranes

132
Q

In ______ _____, vesicles carrying cell wall precursors from the Golgi accumulate at the former site of the metaphase plate.

A

early telophase

133
Q

In M phase, the vesicles fuse to form a membrane-enclosed disk, and polysaccharides form the matrix of a new _____ _____ (cell plate)

A

cell wall

134
Q

Plasmodesmata between the daughter cells are formed as a result of what?

A

incomplete vesicle fusion