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Advanced Cellular and Molecular Biology > Mitosis > Flashcards

Mitosis Flashcards

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1
Q

Sister chromatids are linked by _______, which are composed of 4 subunits: 2 _________ subunits and 2 _________ subunits.

A

Cohesins

Coiled-coil

Globular

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2
Q

What cyclin/CDK complex mediates the transition from G2 to M?

A

Cyclin B/CDK1 or the M-cyclin/CDK complex

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3
Q

Why do cyclin B levels increase steadily through G2? In other words, what causes cyclin B activity to increase?

A

The activity of cyclin A/CDK2 or the S-cyclin/CDK complex

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4
Q

Cyclin B/CDK1 activity is __________ controlled and only increases at the _____ transition.

A

Tightly

G2/M

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5
Q

Cyclin-dependent kinase 1 is subject to two phosphorylations at the onset of mitosis: one _______________, one _____________.

A

Inhibiting

Activating

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6
Q

How many phosphorylations does cyclin-dependent kinase 1 experience at the onset of mitosis?

A

Two

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7
Q

What kinase phosphorylates and inhibits cyclin-dependent kinase 1 at the onset of mitosis?

A

Wee1 kinase

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8
Q

____________ kinase phosphorylates and _________ cyclin-dependent kinase 1 at the onset of ____________.

A

Wee1 kinase

Inhibits

Mitosis

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9
Q

The phosphate added by wee1 kinase must be removed for mitosis to move forward. What phosphatase accomplishes this?

A

Cdc25 phosphatase

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10
Q

What must occur to activate cyclin-dependent kinase 1 so that mitosis can occur?

A

The inhibitory phosphate installed by Wee1 kinase must be removed by Cdc25 phosphatase

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11
Q

Cdc25 phosphatase must be _______________ in order to function.

A

Phosphorylated

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12
Q

Cdc 25 phosphatase is initiatlly activated by high cyclin ___/CDK ___ levels.

A

Cyclin A/CDK2

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13
Q

The majority of activation of Cdc25 phosphatase occurs via phosphorylation by cyclin ___/CDK ___.

A

Cyclin B/CDK1

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14
Q

Phosphorylation of Cdc25 phosphatase by cyclin B/CDK1 initiates a ____________ feedback loop for both Cdc25 and cyclin B/CDK1 activation.

A

Positive

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15
Q

Cyclin B/CDK1 phosphorylate Cdc25 phosphatase, activating it, and _______ kinase, inhibiting it, thereby activating even more cyclin B/CDK1

A

Wee1 kinase

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16
Q

In fission yeast, most growth occurs during ______ phase.

A

G2

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17
Q

Where is Wee1 kinase localized in the cell during mitosis in fission yeast?

A

Mid-point

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18
Q

What inhibits Wee1 kinase at the mid-point of the cell?

A

Cdr2

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19
Q

Pom1 is localized to the ______ of the cell and interferes with cdr2’s ability to inhibit Wee1 kinase.

A

Apex

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20
Q

What protein interferes with Cdr2 and thereby prevents its ability to inhibit Wee1 kinase?

A

Pom1

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21
Q

When cells are small, Pom1 is close enough to prevent Cdr2 from interacting with Wee1 kinasae. But as the cell elongates, _____ moves away from Cdr2 and ______, allowing _______ to bind and inhibit Wee1 kinase, thereby allowing for movement into mitosis.

A

Pom1

Wee1 kinase

Cdr2

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22
Q

When cells are small, _______ is close enough to cdr2, inhibiting its ability to inhibit ________ kinase. As the cell increases in size, ______ moves away from cdr2, which then inhibits __________ kinase and allows ________ to begin.

A

Pom1

Wee1 kinase

Pom1

Wee1 kinase

Mitosis

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23
Q

In Wee1 kinase ___________, cyclin B/CDK1 are not phosphorylated at the inhibitory site, meaning that CDK1 becomes active earlier in GS before sufficient growth has occured. This leads to cell division when the cells are still very _______.

A

Mutants

Small

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24
Q

What four things happen during mitosis?

A
  1. Chromosome condensation
  2. Nuclear envelope breakdown
  3. Mitotic spindle formation
  4. Sister chromatid separation and segregation
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25
Q

Downstream mitotic events of cyclin B/CDK1 are (1) chromosome ________________, (2) nuclear envelope ______________, (3) mitotic ______________ formation, and (4) sister chromatid separation/segregation.

A

Condensation

Breakdown

Spindle

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26
Q

The events of mitosis require both _______________ and ______________ kinases.

A

Polo-like kinase

Aurora kinases

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27
Q

_________________________ of condensins by cyclin B/CDK1 leads to ___________________ of chromosomes.

A

Phosphorylation

Condensation

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28
Q

Which protein is responsible for chromosome condensation?

A

Condensins

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29
Q

What protein phosphorylates condensins?

A

Cyclin B/CDK1

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30
Q

The nuclear ___________________ lines the inner surface of the nuclear envelope.

A

Lamina

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31
Q

The nuclear lamina is composed of three proteins. What are they?

A
  1. Lamin A
  2. Lamin B
  3. Lamin C
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32
Q

What phosphorylates and destabilizes lamins in the nuclear lamina?

A

CDK1

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33
Q

CDK1 _________________ and destrabilizes lamins of the nuclear ______________.

A

Phosphorylates

Lamina

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34
Q

CDK1 phosphorylates both lamins and ___________________.

A

Nuclear pore proteins

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35
Q

Phosphorylation of nuclear pore proteins by _____________ leads to nuclear pore protein ________________.

A

CDK1

Dissociation

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36
Q

In order for mitosis to continue, the nuclear ____________ must be broken down.

A

Envelope

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37
Q

The mitotic spindle arises from what type of cytoskeleton element?

A

Microtubules

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38
Q

What are astral microtubules?

A

Astral microtubules are a subpopulation of microtubules, which only exist during and immediately before mitosis. They are defined as any microtubule originating from the centrosome which does not connect to a kinetochore.

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39
Q

What are kinetochore microtubules?

A

Kinetochore microtubules attach the chromosomes to the spindle pole

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40
Q

What are interpolar microtubules?

A

Interpolar/Polar microtubules are a class of microtubules which also radiate out from the centrosome during mitosis. These microtubules radiate towards the mitotic spindle, unlike astral microtubules

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41
Q

Be familiar with this figure.

A
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42
Q

When does centrosome duplication occur?

A

Beginning of S phase

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43
Q

What cyclin/CDK complex does centrosome duplication require?

A

Cyclin E/CDK2

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44
Q

Centrosome duplication occurs at the beginning of _____ phase and requires cyclin ____/CDK____.

A

S phase

Cyclin E

CDK2

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45
Q

Centrosome separation does not occur until _________ and requires cyclin B/CDK1 and other kinases to occur.

A

Mitosis

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46
Q

Centrosome separation occurs in mitosis and requires cyclin B/CDK__ to occur.

A

Cyclin B/CDK1

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47
Q

Centrosome separation requires _____________ of centrosomal proteins by CDK1, ____________ kinases, and polo-like kinases.

A

Phosphorylation

Aurora kinases

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48
Q

Which three kinases are involved in centrosome separation?

A
  1. CDK1
  2. Aurora kinases
  3. Polo-like kinases
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49
Q

Centrosomal proteins must be _______________ for centrosome separation to occur.

A

Phosphorylated

50
Q

Both _________ and _________ kinase activate kinesin 5.

A

CDK1

Aurora kinase

51
Q

What two kinases phosphorylate and activate kinsein 5?

A

CDK1

Aurora kinase

52
Q

CDK1 and Aurora kinase phosphorylate and activate…?

A

Kinesin 5

53
Q

What is kinesin 5?

A

A bipolar kinesin that functions between interpolar microtubules

54
Q

Kinesin 5 is a ____________ kinesin that functions between ____________ microtubules.

A

Bipolar

Interpolar

55
Q

The GEF for ____ is attached to chromatin.

A

Ran

56
Q

Because ____-GEF is attached to chromatin, a high concentration of ___-G_P develops around the chromatin.

A

Ran-GEF

Ran-GTP

57
Q

High concentrations of Ran-GTP provide the environment required for the ____________ __________ to form near the chromosome.

A

Mitotic spindle

58
Q

Ran activates microtubule ___________ proteins.

A

Stabilizing

59
Q

Motor proteins reposition chromosomes and push the ___________ poles apart.

A

Spindle

60
Q

What does Ran do?

A

It activates microtubule stabilizing proteins

61
Q

The ________________ of each sister chromatid must attach to microtubules from opposite spindle poles for mitosis to occur.

A

Kinetochore

62
Q

There are two layers to the kinetochore: (1) the outer layer and (2) the _________ layer.

A

Inner

63
Q

It is the ____________ layer of the kinetochore that contains the _____ complex, which directly associates with microtubules.

A

Outer layer

Ndc80

64
Q

What part of the kinetochore directly interacts with microtubules?

A

Ndc80 complex

65
Q

What orientation of kinetochore binding is stable?

A

Bi-orientation

66
Q

Is attachment of kinetochore random or unrandom?

A

Random

67
Q

Attachment of kinetochores is a _____________ process.

A

Random

68
Q

Only the ___-orientation of kinetochores is stable.

A

Bi

69
Q

___________ proteins are located in the ________ kinetochore while Aurora B kinase is attached to the inner kitochore.

A

Ndc80 proteins

Outer kinetochore

70
Q

Which kinase is located in the inner kinetochore?

A

Aurora B kinase

71
Q

Phosphorylated or dephosphorylated Ndc80 cannot bind to microtubules?

A

Phosphorylated

72
Q

_________________ Ndc80 proteins cannot bind microtubules.

A

Phosphorylated

73
Q

_________ B kinase phosphorylates ______ complex, and in its phosphorylated state, ______ complex cannot bind microtubules.

A

Aurora B kinase

Ndc80

Ndc80

74
Q

Not all Ndc80 proteins are phosphorylated, and those that are not may attach to microtubules, generating ________ that leads to (1) outer kinetochore proteins pulling away from ___________, (2) microtubules remaing attached to unphosphorylated Ndc80 proteins, and (3) fewer Ndc80 proteins are phosphorylated and more ________________ can attach.

A

Tension

Aurora B kinase

Microtubules

75
Q

At high tension there are _________________ (fewer or more) phosphorylated Ndc80 proteins. At low tension there are (fewer or more) phosphorylated Ndc80 proteins.

A

Fewer

More

76
Q

Be familiar with this figure.

A
77
Q

Cohesins are removed from sister chromatids by the enzyme _______________.

A

Separase

78
Q

Separase is bound by a sequesting protein called _______________.

A

Securin

79
Q

Separase must be released from ________________ and phosphorylated by _______ in order to remove cohesins from sister chromatids.

A

Securin

CDK1

80
Q

What targets securin for degradation?

A

APC/C (anaphase promoting complex or cyclosome)

81
Q

APC/C is a ubiquinating ligase that targets ___________ for degradation.

A

Securin

82
Q

Cdc20 provides substrate recognition for APC/C to recognize securin and target securin for…..?

A

Degradation

83
Q

What provides substrate recogition for APC/C to target securin for degradation?

A

Cdc20

84
Q

What activates APC/C?

A

Phosphorylation by cyclin B/CDK1

85
Q

APC/C is _____________ by cyclin B/CDK1.

A

Phosphorylated and activated

86
Q

Cdc20 provies substrate ________________ for APC/C to target securin.

A

Specificity

87
Q

When does cdc20 become available?

A

When all kinetochores are bound properly by microtubules

88
Q

Why is cdc20 important?

A

It prevents premature separation of sister chromatids

89
Q

The presence of cdc20 is the rate-limiting step for ___________ separation.

A

Sister chromatid

90
Q

Cohesins must be removed from kinetochores by ______________. Separase must be released from ___________, which will release separase when phosphorylated by __________. Securin is then targeted for degradation by APC/C, an E3 ubiqutin ligase, after APC/C has been phosphorylated and activated by cyclin __/CDK1.

A

Separase

Securin

CDK1

Cyclin B/CDK1

91
Q

The spindle asembly checkpoint is the last checkpoint in the _____ cycle.

A

Cell

92
Q

_____________ binds and sequesters Cdc20.

A

Mad2 (closed conformation)

93
Q

Is it the open or close conformation of Mad2 that binds and sequesters cdc20?

A

Closed

94
Q

The Mad1/Mad2 tetramer, closed conformation, binds to the ________________, which serves as a nucleation site to convert cytosolic Mad2 from open to ______ conformation.

A

Kinetochore

Closed

95
Q

What tetramer binds to the kinetochore?

A

Mad1/Mad2

96
Q

What does Mad1/Mad2 accomplish after binding the kinetochore?

A

Converts cytosolic Mad2 from open to closed conformation so that it can then bind and sequester cdc20

97
Q

_______ cytosolic Mad2 binds the Mad1/Mad2 tetramer _________, changing its open conformation to a closed one.

A

Open

Transiently

98
Q

Once in its closed conformation, Mad2 can bind _______ and sequester it. Mad2(closed)/cdc20 then facilitate conversion of free Mad2(open) to Mad2(closed) and its binding to cdc20.

A

cdc20

99
Q

If one kinetochore binds with the Mad1/Mad2 tetramer, all of the ______ in the cell will become bound.

A

Cdc20

100
Q

Once every kinetochore is bound to microtubules, the Mad1/Mad2 tetramers are displaced, enabling a protein called ______ to interact with Mad2/Cdc20 complex.

A

p31

101
Q

Microtubule binding displaces what tetramer?

A

Mad1/Mad2

102
Q

Once the microtubule displaces the Mad1/Mad2 tetramer, p31 disassembles the cdc20/Mad2 complex, allowing cdc20 to provide substrate _______ for APC/C to target _________ for degradation, thereby allowing separase to remove cohesins binding sister chromatids together.

A

Specificity

Securin

103
Q

Prior to microtubule attachment to kinetochores, Mad1/Mad2 in its closed conformation binds the kinetochores and facilitates the conversion of cytosolic ______ to its _______ conformation, thereby enabling ______ to bind and sequester cdc20.

Once microtubules attach to kinetochores, Mad1/Mad2 is displaced, and _____ disassembles the Mad2/cdc20 complex. This frees ______ to provide the substrate specificity required for APC/C to target securin for degradation. Securin must be degraded in order to release __________, which will remove the _______ that bind sister chromatids together.

A

Mad2

Closed

Mad2

p31

cdc20

Separase

Cohesins

104
Q

The spindle assembly checkpoint ensures that sister chromatids do not ___________ prematurely.

A

Separate

105
Q

The spindle assembly checkpoint prevents premature separate of sister chromatids by sequestering all of the _______ in the cell, thereby preventing its ability to target ________ for degradation and to release _______.

A

Cdc20

Securin

Separase

106
Q

The spindle assembly checkpoint is inactivated once microtubules attach to kinetochores, displacing _______________ tetramers. This enables ______ to disassemble the cdc20 from Mad2 (closed) and thereby target securin for degradation by APC/C and release separase to remove the ______ holding sister chromatids together.

A

Mad1/Mad2

p31

Cohesins

107
Q

Cdc20 gets the cell out of _______, and the mitotic exit is finished by _______.

A

Anaphase

Cdh1

108
Q

Cdh1 provides substrate __________ for APC/C in the mitotic exit so that APC/C can ___________ and target multiple proteins for degradation.

A

Specificty

Ubiquinate

109
Q

Cdh1 is phosphorylated and inactivated by cyclin __/CDK__.

A

Cyclin B/CDK1

110
Q

Cdh1 is dephosphorylated and activated by _____.

A

Cdc14

111
Q

As cyclin B/CDK1 is broken down by cdc20/APC/C, the phosphatase activity of _____ takes over.

A

Cdc14

112
Q

In yeast, cdc14 is sequestered in the __________ and ________ but released by separase activity in early anaphase.

A

Nucleolus

Centrosome

113
Q

Cdc14 dephosphorylates _____, leading to the mitotic _____.

A

Cdh1

Exit

114
Q

Cdc14 dephosphorylates and activates CKIs (CDK inhibitory proteins), which bind and inhibit cyclin ___/CDK__ to prevent early entry into S phase.

A

Cyclin A/CDK2

115
Q

CKIs were phosphorylated and deactivated by cyclin E/CDK2 from ____ phase. This phosphorylation was then recognized by ______ complex, an E3 ubiquinating ligase.

A

G1/S phase

SCF complex

116
Q

Phosphorylated CKIs are targeted for degradation by SCF. Once dephosphorylated by ______, CKIs are no longer targets for SCF and can bind cyclin A/CDK2, preventing re-entry into S-phase and ensuring re-establisment of _____ phase.

A

Cdc14

G1 phase

117
Q

Cdc14 is crucial in re-establishing what phase of the cell cycle?

A

G1 phase

118
Q

While cdc14 is sequestered for most of mitosis, protein phosphatases _____ and ____ are constitutively activated.

A

PP1

PP2A

119
Q

PP1 and PP2A dephosphorylate previously phosphorylated targets of CDK1, ________ kinase, and Aurora kinases.

A

Polo-like

120
Q
A

Advanced Cellular and Molecular Biology (7 decks)

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