Cell Cycle Control and Cell Division Flashcards

1
Q

The cell-cycle involves DNA replication and dividing the cell to
create

A

two identical daughter cells

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2
Q

The cell-cycle control system triggers the major events of the

A

cell cycle

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3
Q

As the cell cycle proceeds a series of (2) ensure

that each phase is complete before the next one begins

A

transitions or checkpoints

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4
Q

There are - major checkpoints in eukaryotic cells

A

3

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5
Q

The cell-cycle control machinery therefore controls

A

cell proliferation

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6
Q

— is essentially inappropriate proliferation

A

Cancer

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7
Q

Many of the genes (proteins) involved in cell-cycle regulation are
critical determinants of

A

cancer progression

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8
Q

The system depends on cyclically activated

A

cyclin-dependent protein kinases (Cdks)

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9
Q

The cell-cycle control system depends on

A

cyclical proteolytic events

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10
Q

The cell-cycle control depends on

A

transcriptional regulation

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11
Q

The Cell-Cycle Control System triggers the events that occur in each phase of
the

A

cell cycle

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12
Q

The Cell-Cycle Control System ensures the proper (3)

A

timing, order and fidelity of

the events

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13
Q

The Cell-Cycle Control System responds to (2)

A

intracellular and extracellular signals

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14
Q

The Cell-Cycle Control System arrests the cycle whenever the cell (2)

A

fails to
complete an essential cell-cycle process or
encounters unfavorable intracellular or
extracellular conditions

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15
Q

Control of the Cell-cycle by (2)

A

Cyclins and Cyclin-Dependent Protein Kinases (Cdks)

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16
Q

Cyclin-dependent kinase (Cdk) requires the binding of — and subsequent specific — to become an active enzyme

A

cyclin

phosphorylation

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17
Q

In the absence of cyclin, Cdk is in an — state

A

inactive

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18
Q

The concentrations of the three major cyclin proteins

— during the cell cycle

A

oscillate

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19
Q

their expression is —

to promote transitions through the cell cycle

A

induced

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20
Q

The concentrations of the Cdk…

A

do not change

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21
Q

constitutive expression

A

concentration do not change

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22
Q

The appearance and disappearance of the various cyclins

are critical for determining the

A

transitions from one phase

of the cell-cycle to the next

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23
Q

in addition, the Anaphase-Promoting Complex or

Cyclosome (APC/C) initiates the

A

metaphase to anaphase

transition

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24
Q

G1-Cdk cyclin

A

D

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25
G1/S-Cdk cyclin
E
26
S-Cdk cyclin
A
27
M-Cdk cyclin
B
28
In the inactive state the catalytic or active site of the cyclin-dependent kinase is blocked by the presence of a region called the
T-loop
29
Binding | of the specific cyclin to its cognate cyclin-dependent kinase leads to
a movement of the T-loop away from the active site, leading to partial activation
30
Cdk-activating kinase (CAK) can then
phosphorylate the T- loop at a threonine residue in the T-loop resulting in full activation of the cyclin-Cdk
31
Each cyclin partner is important for | determining which specific targets are
subsequently phosphorylated by the Cdk | subunit
32
Each cyclin-Cdk can induce different effects at | different times in the cell-cycle based upon the (3)
relative presence, absence or abundance of each specific target, which can change depending upon the phase of the cell cycle
33
Activation of the --- --- is prerequisite for downstream events, however the activity of each complex is finely regulated by additional mechanisms
Cyclin-Cdk complex
34
Just as mutations that alter cyclin or Cdk function can lead to misregulation of the cell cycle, so too can mutations that
disrupt any of these regulatory mechanisms create the possibility that a cancer of some type may occur
35
The activity of cyclin-Cdk is further regulated by
Wee1 kinase | Cdc25
36
Wee1 kinase
further phosphorylates Cdk and renders it inactive
37
Cdc25 phosphatase
dephosphorylates and restores activity
38
APC/C is a member of the --- --- family of proteins
ubiquitin ligase
39
APC/C catalyzes the (2)
ubiquitylation and degradation of securin and the S- and M-cyclins
40
--- is involved in protecting the protein linkages that hold the sister chromatids together
Securin
41
Securin degradation leads to
activation of a protease that then separates | the sisters and unleashes anaphase
42
Degradation of the S- and M-cyclins leads to inactivation of the
Cdks
43
loss of the | Cdks means that their targets can be
dephosphorylated by various phosphatases | that are present in anaphase, which completes M phase
44
APC/C is activated in
mid-mitosis and remains active in G1
45
APC/C is activated in mid-mitosis and remains active in G1, which provides a period in which Cdk is ---
inactive
46
When the G1/S-Cdks are activated in late G1, --- is | turned off
APC/C
47
This allows for --- accumulation to start the next cell-cycle
cyclin
48
APC/C activity changes during the cell cycle due to its interactions with --- in anaphase and --- from late mitosis through early G1
Cdc20 | Cdh1
49
Control of the Cell-Cycle by ---
Proteolysis
50
SCF
Ubiquitin ligase like APC/C
51
SCF contains - subunits
3 | S, C and F
52
SCF
Ubiquitylates Cdk inhibitor (CKI) proteins in | late G1 such as p27
53
Ubiquitylation of proteins is a key step in the | initiation of many proteins “marked” for
degradation by the proteasome complex
54
--- is a CKI family member that binds to the active cyclin-Cdk complex
p27
55
p27 binds to both the
cyclin and the Cdk subunits
56
This distorts the active | site of the --- and p27 also inserts into the ATP-binding site, further
Cdk | inhibiting the enzyme activity
57
SCF associates with an --- protein that is required for
F-box binding to specific protein targets
58
2 additional proteins (2) assist in the addition of multiple ubiquitin molecules to the CKI and this targets the protein for degradation in the proteosome complex
E1 and E2
59
Cyclin gene expression is regulated and specific cyclins genes are induced (turned on) as
the cell cycle transitions from one phase to | the next
60
Many other key regulatory proteins are | regulated at the --- level
transcriptional
61
CAK
phosphorylates an activating site in Cdks
62
Wee1 kinase
phosphorylates inhibitory sites in cdks; primarily involved in suppressing cdk1 activity before mitosis
63
cdc25 phosphatase
removes inhibitory phosphates from cdks
64
p27
suppresses G1/S-cdk and s-cdk activities in G1
65
p21
suppresses G1-S-cdk and S-cdk activities following DNA damage
66
p16
suppresses G1-cdk activity in G1
67
APC/C
catalyzes ubiquitination of regulatory proteins involved primarily in exit from mitosis, including securing and S and M cyclins; regulated by association with activating subunits
68
cdc20
APCC activating subunit in all cells; triggers initial activation of APCC at metaphase to anaphase transition; stimulated by M-cdk activity
69
cdh1
APCC activating subunit that maintains APCC activity after anaphase and throughout G1; inhibited by Cdk activity
70
SCF
catalyzes ubiquitylation of regulatory proteins involved in G1 control, including some CKIs
71
Cell-Cycle Control
The central component of the control system is the series of cyclin-Cdk complexes that regulate transitions through the various phases
72
``` The complexes are also regulated by various inhibitory mechanisms, which provide information about the (3) ```
extracellular environment, DNA or cell | damage and whether each step in the cell-cycle has been properly completed
73
G0 represents a
resting or quiescent state
74
Cells can remain in G0 for
days to weeks or | longer before resuming proliferation
75
Cells can enter G0...
permanently until the cell | dies
76
Cells enter G0 from a cell-cycle checkpoint in the
G1 phase
77
G0 generally occurs due to (2)
lack of growth factors or nutrients
78
When does G0 occur in cells?
when they reach maturity | wells become terminally differentiated, such as nerve cells, heart muscle cells, or bone osteocytes
79
The --- complex binds exclusively to deacteylated histone H4
dREAM
80
what causes cells to move into G0?
dREAM complex
81
--- associated co-activators promote transcription
E2F
82
co-repressors of either | E2F and pRB lead to histone modifications that result in (2)
histone compaction and | suppression of gene expression