ch.18 Flashcards
1
Q
Each parental cell gives rise to two _______ cells on completion of a cycle of cell division.
A
daughter
2
Q
Eukaryotic cells progression through the cell cycle is controlled by what?
A
protein kinases
3
Q
Defects in cell cycle regulations is a common cause of what?
A
the abnormal proliferation of cancer cells
4
Q
The division cycle of most cells consists of 4 coordinated processes, what are they?
A
- cell growth
- DNA replication
- distribution of the duplicated chromosomes to daughter cells
- cell division
5
Q
In prokaryotes, chromosomes is ______ and the daughter DNA is separated into the two daughter cells.
A
duplicated
6
Q
What are the 4 cell cycle phases in eukaryotes?
A
M, G1, S, and G2
7
Q
What is the M phase?
A
mitosis (nuclear division)
8
Q
The M phase usually ends with what?
A
cell division (cytokinesis)
9
Q
What is Interphase?
A
period between mitoses
10
Q
What is interphase divided into?
A
G1, S, and G2
11
Q
What is G1 phase?
A
- Interval between mitosis and DNA replication
- The cell is metabolically active and growing
12
Q
What happens in S phase?
A
DNA replication
13
Q
What happens in G2 phase?
A
- cell growth continues
- proteins are synthesized in preparation for mitosis
14
Q
Early embryos may have cell cycles of ____ minutes
A
30
15
Q
In early embryos, there is no what?
A
no growth (G1 or G2) phase
16
Q
Animal cells in ____ are diploid.
A
G1
17
Q
diploid = _____ DNA content
A
2n
18
Q
In S phase, replication increases the DNA content to ____
A
4n
19
Q
How can DNA content be determined?
A
by incubation of cells with a fluorescent dye that binds to DNA
20
Q
What is fluorescence intensity of individual cells measured in?
A
a flow cytometer or fluorescence-activated cell sorter
21
Q
The progression of cell division is regulated by what?
A
extracellular and internal signals
22
Q
What are the control points that regulate cellular processes?
A
growth, DNA replication, mitosis
23
Q
What is a major control point?
A
START
24
Q
what does START control?
A
controls progression from G1 to S
25
What happens once cells pass START?
committed to entering S phase and undergoing one division cycle
26
What is passage through START highly regulated by?
external signals, such as nutrient availability and cell size
27
What happens if there is a shortage of nutrients?
yeast cells can arrest the cycle at START and enter a resting phase
28
Yeast cells must reach a minimum ____ to pass START.
size
29
Small daughter cells of budding yeasts spend a longer time in ___ and grow more than the large mother cell.
G1
30
Passing through the restriction point commits the cell to what phases?
S and M phase
31
If appropriate growth factors are not present in G1, what happens?
Progression stops at the restriction point and cells enter G0
32
What is G0?
a resting stage
33
Skin fibroblasts are arrested in G0 until stimulated by what?
platelet-derived growth factor to proliferate and repair wound damage
34
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?
the fission yeast schizosaccharomyces pombe cell cycle
35
Cell cycle control in G2 also occurs in animal _____
oocytes
36
How long do vertebrate oocytes remain arrested in G2 for?
long periods (decades in humans)
37
In vertebrate oocytes, progression to M phase is triggered by what?
hormonal stimulation
38
Coordination of the cell cycle phases is dependent on a series of cell cycle _____
checkpoints
39
What do cell cycle checkpoints do?
prevent entry into the next phase until events of the preceding phase have been completed
40
DNA damage checkpoints ensures what?
- that damaged DNA is not replicated and passed on to daughter cells
- cell cycle is arrested until DNA is repaired or replicated
41
What does the spindle assembly checkpoint do?
stops mitosis at metaphase if chromosomes are not properly aligned on the spindle
42
What triggers the major eukaryotic cell cycle transitions?
a conserved set of protein kinases
43
The studies of frog oocytes contributed to identification of what?
frog oocytes are arrested in G2 until hormonal stimulation triggers entry into M phase
44
What was cytoplasmic factor was responsible for the study of frog oocytes discovery?
maturation promoting factor (MPF)
45
MPF is also present in what?
somatic cells
46
MPF incudes what?
entry into M phase
47
MPF appeared to act as what?
a general regulator of the transition from G2 to M
48
The genetic analyses of yeast determined what?
temperature-sensitive mutants that were defective in cell cycle progression
49
cell division cycle mutants (cdc) genes are required for what?
passage through START and entry into mitosis
50
What do cell division mutants (cdc) do?
encode protein kinases
51
what is Cdk1?
the protein kinase that is a cell cycle regulator conserved in all eukaryotes
52
Protein synthesis in early sea urchin embryos discovered what?
two proteins (cyclins) that accumulate throughout interphase but rapidly degrade at the end of mitosis
53
When the 3 experimental approaches to cell cycle regulators converged, how were the components determined to function together?
- MPF was composed of Cdk1 and cyclin B
- cyclin B is a regulatory subunit required for catalytic activity of the Cdk1 protein kinase
54
Research has established that _____ and _____ are members of protein families.
Cdk1 and cyclin B
55
In yeasts, what does Cdk1 control?
G2 to M transition in association with mitotic B-type cyclins
56
Cdk1 controls passage through START and entry into mitosis in association with what?
G1 cyclins or Cln's
57
What does Cdk stand for?
cyclin-dependent kinases
58
Studies of Cdk's and cyclins in genetically modified mice reveal high level of what?
plasticity
59
What does the high level of plasticity of Cdk's and cyclins allow them to do?
compensate for the loss of either Cdk's or cyclins
60
_____ is capable of substituting for all the other CDk's
Cdk1
61
What are the 2 families of Cdk inhibitors in mammalian cells?
Ink4 and Cip/Kip
62
what are one link between growth factor signaling and cell cycle progression?
D-type cyclins
63
Growth factors stimulate cyclin D synthesis through what pathway?
the Ras/Raf/MEK/ERK pathway
64
Cyclin D1 is synthesized as longa as ____ ______ are present.
growth factors
65
Cyclin D1 is rapidly degraded due to what?
APC/C ubiquitin ligase
66
As long as growth factors are present through ____, Cdk4, 6/cyclin D complexes drive cells through the restriction point.
G1
67
Defects in cyclin D regulation could contribute to what?
the loss of growth regulation characteristic of cancer cells
68
Many human cancers arise as a result of defects in what?
cell cycle regulation
69
What is Rb?
a substrate protein of Cdk4, 6/cyclin D complexes
70
What substrate protein is frequently mutated in many human tumors?
Rb
71
What was Rb first identified in?
retinoblastoma
72
Rb is the prototype _____ _____ gene
tumor suppressor
73
The inactivation of Rb leads to what?
tumor development
74
Proteins encoded by tumor suppressor genes act as what?
brakes that slow down cell cycle progression
75
In G0 or early G1 \, Rb binds to what?
E2F transcription factors
76
When Rb binds to E2F, what does it do?
suppresses expression of genes involved in cell cycle progression
77
Progression through the restriction point is mediated by the activation of what?
Cdk2/cyclin E complexes
78
In G0 and early G1, Cdk2/cyclin E is inhibited by what?
p27 (Cip/Kip family)
79
How is the inhibition of Cdk2 relieved?
by multiple mechanisms as cells progress through G1
80
What reduces transcription and translation of p27?
growth factor signaling via Ras/Raf/MEK/ERk and PI 3-kinase/Akt pathways
81
When Cdk2 becomes activated, it phosphorylates ____ and targets it for ubiquitylation.
p27
82
What is inhibited by Cdk2?
APC/C ubiquitin ligase
83
When are high levels of cyclins maintained through S and G2?
when APC/C ubiquitin ligase is inhibited by Cdk2
84
what initiates S phase by activating DNA synthesis at replication origins?
Cdk2/cyclin E
85
MCM helicase and origin recognition complex (ORC) proteins bind to what during G1?
replication origins
86
Cdk2/cyclin E activates the _____ by phosphorylating activating proteins.
ORC
87
What does the inhibition of APC/C (by Cdk2/CycE) lead to?
the activation of protein kinase DDK
88
What does the protein kinase DDK phosphorylate directly?
MCM proteins
89
What does the high activity of Cdk's during S, G2, and M phases prevent?
MCM proteins from reassociating with replication origins
90
Pre-replication complexes can only reform when?
during G1 when Cdk activity is low
91
Cell cycle arrest at DNA damage checkpoints is mediated by what?
protein kinases ATM and ATR
92
ATM and ATR activate a signaling pathway that leas to what?
cell cycle arrest, DNA repair, and programmed cell death
93
What phosphorylates and inhibits Cdc25 phosphatases?
Chk1 and Chk2
94
What are requires to activate Cdk1 and Cdk2?
Cdc25 phosphatases
95
Inhibition of Cdk2 results in what?
cell cycle arrest in G1 and S
96
What does inhibition of Cdk1 result in?
arrest in G2
97
In mammalian cells, arrest is also mediated by what protein?
p53
98
p53 is phosphorylated by what?
ATM and Chk2
99
Increased levels of p53 leads to what?
induction of Cdk inhibitor p21
100
what does p21 inhibit?
Cdk2/cyclin E or A complexes
101
When Cdk2/cyclin E or A complexes are inhibited, what does that lead to?
cell cycle arrest
102
what gene is frequently mutated in about 50% human cancer?
p53
103
Around 100% of cancers involve a defect in the ____ pathway.
p53
104
loss of ____ prevents cell cycle arrest in response to DNA damage, so the damaged DNA is replicated and passed on to daughter cells.
p53
105
What happens in chromatin condensation?
phosphorylation of condensins and cohesins
106
what happens in nuclear envelope breakdown?
phosphorylation of lamins, nuclear pore complexes, and inner nuclear membrane proteins
107
what happens in fragmentation of golgi apparatus?
phosphorylation of golgi matrix proteins
108
What happens in spindle formation?
phosphorylation of centrosome, kinetochore, and microtubule-associated proteins
109
Golgi breakdown is mediated by phosphorylation of proteins by _____ and _____ kinases.
Cdk1 and Polo-like
110
Reorganization of the cytoskeleton and formation of the mitotic spindle results from what?
the dynamic instability of microtubules
111
What are centrosome maturation and spindle assembly are driven by?
Aurora and Polo-like kinases at the centrosomes
112
In M phase, microtubule turnover rate ______, resulting in depolymerization and shrinkage of the interphase microtubules.
increases
113
In M phase, the number of microtubules radiating from the centrosomes ________.
increases
114
In the M phase, the breakdown of the nuclear envelope allows spindle microtubules to what?
attach to chromosomes at the kinetochores
115
In M phase, chromosomes in prometaphase do what due to activity of microtubule motors at the kinetochore and centrosomes.
shuffle back and forth
116
In the M phase, the balance of forces acting on the chromosomes leads to what?
their alignment on the metaphase plate
117
What does the spindle consist of?
kinetochore, polar microtubules, astral microtubules, and chromosomal microtubules
118
At the spindle assembly checkpoint, progression to anaphase is mediated by activation of ________
APC/C ubiquitin ligase
119
The presence of even one unaligned chromosome is sufficient to prevent what?
activation of the APC/C
120
Unattached kinetochores leads to the assembly of the ________ _______ _______.
mitotic checkpoint complex (MCC)
121
In the M phase, once all chromosomes are aligned on the spindle, the inhibitory complex is no longer formed and APC/C is ______
activated
122
APC/C ________ cyclin B and securin.
ubiquitylates
123
Cyclin B and securin inactivates what?
Cdk1 and separase
124
What breaks the link between sister chromatids, allowing them to segregate and move to opposite spindle poles?
separase degrades cohesin
125
Separation of chromosomes during anaphase proceeds by the action of what?
motor proteins associated with the spindle microtubules
126
APC/C also triggers degradation of Aurora and Polo-like kinases, allowing the cell do what?
to exit mitosis and return to interphase
127
What triggers cytokinesis?
inactivation of Cdk1
128
Cytokinesis of yeast and animal cells is mediated by a _____ _____ of actin and myosin II filaments that forms beneath the plasma membrane
contractile ring
129
Ring formation is activated by ______ and _______ kinases.
Aurora and Polo-like
130
What pulls the plasma membrane inward?
Contraction of the actin-myosin filaments, eventually pinching the cell in half
131
In plant cells, how does cytokinesis proceed?
by formation of new cell walls and plasma membranes
132
In ______ _____, vesicles carrying cell wall precursors from the Golgi accumulate at the former site of the metaphase plate.
early telophase
133
In M phase, the vesicles fuse to form a membrane-enclosed disk, and polysaccharides form the matrix of a new _____ _____ (cell plate)
cell wall
134
Plasmodesmata between the daughter cells are formed as a result of what?
incomplete vesicle fusion
