Mitosis Flashcards

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
Downstream mitotic events of cyclin B/CDK1 are (1) chromosome \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, (2) nuclear envelope \_\_\_\_\_\_\_\_\_\_\_\_\_\_, (3) mitotic ______________ formation, and (4) sister chromatid separation/segregation.
Condensation Breakdown Spindle
26
The events of mitosis require both _______________ and ______________ kinases.
Polo-like kinase Aurora kinases
27
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ of condensins by cyclin B/CDK1 leads to ___________________ of chromosomes.
Phosphorylation Condensation
28
Which protein is responsible for chromosome condensation?
Condensins
29
What protein phosphorylates condensins?
Cyclin B/CDK1
30
The nuclear ___________________ lines the inner surface of the nuclear envelope.
Lamina
31
The nuclear lamina is composed of three proteins. What are they?
1. Lamin A 2. Lamin B 3. Lamin C
32
What phosphorylates and destabilizes lamins in the nuclear lamina?
CDK1
33
CDK1 _________________ and destrabilizes lamins of the nuclear \_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Phosphorylates Lamina
34
CDK1 phosphorylates both lamins and \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Nuclear pore proteins
35
Phosphorylation of nuclear pore proteins by _____________ leads to nuclear pore protein \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
CDK1 Dissociation
36
In order for mitosis to continue, the nuclear ____________ must be broken down.
Envelope
37
The mitotic spindle arises from what type of cytoskeleton element?
Microtubules
38
What are astral microtubules?
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**.
39
What are kinetochore microtubules?
Kinetochore microtubules attach the chromosomes to the spindle pole
40
What are interpolar microtubules?
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
41
Be familiar with this figure.
42
When does centrosome duplication occur?
Beginning of S phase
43
What cyclin/CDK complex does centrosome duplication require?
Cyclin E/CDK2
44
Centrosome duplication occurs at the beginning of _____ phase and requires cyclin \_\_\_\_/CDK\_\_\_\_.
S phase Cyclin E CDK2
45
Centrosome separation does not occur until _________ and requires cyclin B/CDK1 and other kinases to occur.
Mitosis
46
Centrosome separation occurs in mitosis and requires cyclin B/CDK\_\_ to occur.
Cyclin B/CDK1
47
Centrosome separation requires _____________ of centrosomal proteins by CDK1, ____________ kinases, and polo-like kinases.
Phosphorylation Aurora kinases
48
Which three kinases are involved in centrosome separation?
1. CDK1 2. Aurora kinases 3. Polo-like kinases
49
Centrosomal proteins must be _______________ for centrosome separation to occur.
Phosphorylated
50
Both _________ and _________ kinase activate kinesin 5.
CDK1 Aurora kinase
51
What two kinases phosphorylate and activate kinsein 5?
CDK1 Aurora kinase
52
CDK1 and Aurora kinase phosphorylate and activate...?
Kinesin 5
53
What is kinesin 5?
A **bipolar** kinesin that functions between *interpolar* microtubules
54
Kinesin 5 is a ____________ kinesin that functions between ____________ microtubules.
Bipolar Interpolar
55
The GEF for ____ is attached to chromatin.
Ran
56
Because \_\_\_\_-GEF is attached to chromatin, a high concentration of \_\_\_-G\_P develops around the chromatin.
Ran-GEF Ran-GTP
57
High concentrations of Ran-GTP provide the environment required for the ____________ \_\_\_\_\_\_\_\_\_\_ to form near the chromosome.
Mitotic spindle
58
Ran activates microtubule ___________ proteins.
Stabilizing
59
Motor proteins reposition chromosomes and push the ___________ poles apart.
Spindle
60
What does Ran do?
It activates microtubule stabilizing proteins
61
The ________________ of each sister chromatid must attach to microtubules from opposite spindle poles for mitosis to occur.
Kinetochore
62
There are two layers to the kinetochore: (1) the outer layer and (2) the _________ layer.
Inner
63
It is the ____________ layer of the kinetochore that contains the _____ complex, which directly associates with microtubules.
Outer layer Ndc80
64
What part of the kinetochore directly interacts with microtubules?
Ndc80 complex
65
What orientation of kinetochore binding is stable?
Bi-orientation
66
Is attachment of kinetochore random or unrandom?
Random
67
Attachment of kinetochores is a _____________ process.
Random
68
Only the \_\_\_-orientation of kinetochores is stable.
Bi
69
\_\_\_\_\_\_\_\_\_\_\_ proteins are located in the ________ kinetochore while Aurora B kinase is attached to the inner kitochore.
Ndc80 proteins Outer kinetochore
70
Which kinase is located in the inner kinetochore?
Aurora B kinase
71
Phosphorylated or dephosphorylated Ndc80 cannot bind to microtubules?
Phosphorylated
72
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Ndc80 proteins cannot bind microtubules.
Phosphorylated
73
\_\_\_\_\_\_\_\_\_ B kinase phosphorylates ______ complex, and in its phosphorylated state, ______ complex cannot bind microtubules.
Aurora B kinase Ndc80 Ndc80
74
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.
Tension Aurora B kinase Microtubules
75
At high tension there are _________________ (fewer or more) phosphorylated Ndc80 proteins. At low tension there are (fewer or more) phosphorylated Ndc80 proteins.
Fewer More
76
Be familiar with this figure.
77
Cohesins are removed from sister chromatids by the enzyme \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Separase
78
Separase is bound by a sequesting protein called \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Securin
79
Separase must be released from ________________ and phosphorylated by _______ in order to remove cohesins from sister chromatids.
Securin CDK1
80
What targets securin for degradation?
APC/C (anaphase promoting complex or cyclosome)
81
APC/C is a ubiquinating ligase that targets ___________ for degradation.
Securin
82
Cdc20 provides substrate recognition for APC/C to recognize securin and target securin for.....?
Degradation
83
What provides substrate recogition for APC/C to target securin for degradation?
Cdc20
84
What activates APC/C?
Phosphorylation by cyclin B/CDK1
85
APC/C is _____________ by cyclin B/CDK1.
Phosphorylated and activated
86
Cdc20 provies substrate ________________ for APC/C to target securin.
Specificity
87
When does cdc20 become available?
When all kinetochores are bound properly by microtubules
88
Why is cdc20 important?
It prevents premature separation of sister chromatids
89
The presence of cdc20 is the rate-limiting step for ___________ separation.
Sister chromatid
90
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.
Separase Securin CDK1 Cyclin B/CDK1
91
The spindle asembly checkpoint is the last checkpoint in the _____ cycle.
Cell
92
\_\_\_\_\_\_\_\_\_\_\_\_\_ binds and sequesters Cdc20.
Mad2 (closed conformation)
93
Is it the open or close conformation of Mad2 that binds and sequesters cdc20?
Closed
94
The Mad1/Mad2 tetramer, closed conformation, binds to the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, which serves as a nucleation site to convert cytosolic Mad2 from open to ______ conformation.
Kinetochore Closed
95
What tetramer binds to the kinetochore?
Mad1/Mad2
96
What does Mad1/Mad2 accomplish after binding the kinetochore?
Converts cytosolic Mad2 from open to closed conformation so that it can then bind and sequester cdc20
97
\_\_\_\_\_\_\_ cytosolic Mad2 binds the Mad1/Mad2 tetramer \_\_\_\_\_\_\_\_\_, changing its open conformation to a closed one.
Open Transiently
98
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.
cdc20
99
If one kinetochore binds with the Mad1/Mad2 tetramer, all of the ______ in the cell will become bound.
Cdc20
100
Once every kinetochore is bound to microtubules, the Mad1/Mad2 tetramers are displaced, enabling a protein called ______ to interact with Mad2/Cdc20 complex.
p31
101
Microtubule binding displaces what tetramer?
Mad1/Mad2
102
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.
Specificity Securin
103
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.
Mad2 Closed Mad2 p31 cdc20 Separase Cohesins
104
The spindle assembly checkpoint ensures that sister chromatids do not ___________ prematurely.
Separate
105
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 \_\_\_\_\_\_\_.
Cdc20 Securin Separase
106
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.
Mad1/Mad2 p31 Cohesins
107
Cdc20 gets the cell out of \_\_\_\_\_\_\_, and the mitotic exit is finished by \_\_\_\_\_\_\_.
Anaphase Cdh1
108
Cdh1 provides substrate __________ for APC/C in the mitotic exit so that APC/C can ___________ and target multiple proteins for degradation.
Specificty Ubiquinate
109
Cdh1 is phosphorylated and *inactivated* by cyclin \_\_/CDK\_\_.
Cyclin B/CDK1
110
Cdh1 is dephosphorylated and *activated* by \_\_\_\_\_.
Cdc14
111
As cyclin B/CDK1 is broken down by cdc20/APC/C, the phosphatase activity of _____ takes over.
Cdc14
112
In yeast, cdc14 is sequestered in the __________ and ________ but released by separase activity in early anaphase.
Nucleolus Centrosome
113
Cdc14 dephosphorylates \_\_\_\_\_, leading to the mitotic \_\_\_\_\_.
Cdh1 Exit
114
Cdc14 dephosphorylates and activates CKIs (CDK inhibitory proteins), which bind and inhibit cyclin \_\_\_/CDK\_\_ to prevent early entry into S phase.
Cyclin A/CDK2
115
CKIs were phosphorylated and deactivated by cyclin E/CDK2 from ____ phase. This phosphorylation was then recognized by ______ complex, an E3 ubiquinating ligase.
G1/S phase SCF complex
116
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.
Cdc14 G1 phase
117
Cdc14 is crucial in re-establishing what phase of the cell cycle?
G1 phase
118
While cdc14 is sequestered for most of mitosis, protein phosphatases _____ and ____ are constitutively activated.
PP1 PP2A
119
PP1 and PP2A dephosphorylate previously phosphorylated targets of CDK1, ________ kinase, and Aurora kinases.
Polo-like
120