Cell Cycle Regulation Flashcards

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1
Q

Each cell cycle is coordinated with the timing of (3)

A

1) DNA replication
2) Cell Division
3) Growth

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2
Q

What controls cell progression cycle?

A

Regulatory proteins

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3
Q

If the coordination of cell cycle phases FAILS…

A

Daughter cells may contain an incomplete copy of the genome or be too small (leading to cell death)

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4
Q

The Cell Cycle

A

1) G1 Phase
2) S Phase
3) G2 Phase
4) M Phase

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5
Q

G1 Phase

A

AKA “Gap 1” or Growth 1

–> Cell growth occurs and cell prepares for DNA replication

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6
Q

S Phase

A

AKA Synthesis Phase

–> Synthesis (replication) of DNA occurs

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7
Q

G2 Phase

A

AKA “Gap 2” or Growth 2

–> Cell growth occurs and cell prepares for chromosomal segregation

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8
Q

M Phase

A

AKA Mitotic Phase

–> Mitosis occurs followed by cytokinesis

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9
Q

G0 Phase

A

“Quiescent/Quiet” Phase
–> A non-dividing state: An exit from the cell cycle

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10
Q

Most human cells are in what phase?

A

G0

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11
Q

LOOK AT GRAPHS with the 2 lines showing total cell mass and DNA content over a cell cycle

A
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12
Q

How long does it take one cell to go through one cell cycle?

A

It depends on the cell type

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13
Q

Cells that divide frequently

A

Skin Cells

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14
Q

Cells that have the ability to divide but only do so when they must

A

Liver Cells

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15
Q

Cells that rarely/never divide past maturity

A

Nerve and muscle cells

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16
Q

Cells that stop and start dividing based on conditions

A

Cells involved in wound repair

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17
Q

What was the main research question regarding the cell cycle control system?

A

What tells a cell whether to progress through the cell cycle or stop?

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18
Q

Determining the cell cycle control system STUDY:

2 hypotheses

A

1) Each cell cycle EVENT triggers the next event

2) Each event in the cell cycle is driven by specific molecules present in the cell

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19
Q

Determining the cell cycle control system STUDY:

Experiment Design + Results

A

Experiment #1

–> Fused G1 cell with S cell === G1 cell entered S-phase!

Experiment #2

–> Fused G1 cell with M cell
=== G1 cell entered M-Phase (without going through S-phase first; immediately began dividing)

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20
Q

Determining the cell cycle control system STUDY:

Main findings + Conclusion

A

Fusing a G1 cell with a cell in M or S phase caused the G1 cell to initiate cell division or DNA replication

Conclusion = Diffusable molecules trigger a cell to enter a later phase of the cell cycle (induces different phases)

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21
Q

Cell Cycle Control System

A

A cyclically operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle

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22
Q

The cell cycle control system relies on…

A

Internal and External signals for regulation of the cycle at checkpoints

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23
Q

The cell cycle control system has two types of mechanisms:

A

1) Mechanisms that REPRESS cell cycle progression

2) Mechanisms that INDUCE cell cycle progression

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24
Q

Checkpoints

A

“Molecular brakes” –> Can halt the cell cycle

–> A control point where stop and go-ahead signals can regulate the cycle

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25
Q

Signals registered at the checkpoints indicate…

A

if key processes have been completed SUCCESSFULLY

and therefore, whether or not it is safe to move forward

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26
Q

The major checkpoints

A

1) G1 checkpoint

2) G2 checkpoint

3) M checkpoint

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27
Q

G1 Checkpoint

A

AKA START or Restriction Point (The most important checkpoint)

–> Checkpoint that halts or allows for progression into the S phase

–> Cell decides whether to continue on to division, delay division, or enter G0 state

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28
Q

G1 Checkpoint checks for (4):

A

Checks for FAVORABLE CONDITIONS

1) Cell size
2) Nutrient/Energy (does cell have what it needs to divide?)
3) Growth Factors (Molecular signals)
4) DNA integrity

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29
Q

If the cell receives a GO-AHEAD signal at G1 checkpoint…

A

The cell WILL DIVIDE: It has committed to dividing

–> No matter whether it gets delayed in subsequent or whether it is successful or not, the cell will progress to division

–> Only way out: APOPTOSIS

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30
Q

If the cell does NOT receive a GO-AHEAD signal at G1 checkpoint…

A

The cell will enter the G0 state (exits the cell cycle)

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31
Q

G2 Checkpoint

A

“DNA Damage” or “ENTER M-Phase” Checkpoint

–> The point between G2 and M phase: Can delay the progression into mitosis if needed (if DNA errors are found)

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32
Q

G2 Checkpoint Checks for (2):

A

Any issues with the DNA:

1) DNA Damage
2) DNA replication completeness

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33
Q

The G2 checkpoint will HALT the cell cycle if…

A

DNA damage is found

–> Will not proceed until repairs are made

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34
Q

The G2 checkpoint will progress the cell cycle if…

A

No errors in the DNA are found

–> Pushing the cell into the M-Phase

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35
Q

If DNA errors are irreparable, what occurs at the G2 checkpoint?

A

The cell may induce apoptosis

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36
Q

The “question” G2 checkpoint asks the cell

A

Are you ready for mitosis?

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37
Q

The “question” G1 checkpoint asks the cell

A

Are conditions favorable and appropriate to begin cell division process?

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38
Q

M Checkpoint

A

“Metaphase” or “Mitotic Spindle” Checkpoint

–> Checkpoint occurs between metaphase and anaphase

–> Will delay anaphase until all necessary conditions are met

39
Q

M Checkpoint checks for:

A

1) Proper attachment of sister chromatids to the microtubules from the mitotic spindle at the metaphase plate

40
Q

Mitosis is paused at the M Checkpoint if…

A

Any chromosomes are found to be improperly attached to or not attached at all to the microtubules

41
Q

Anaphase begins at the M checkpoint if…

A

All chromosomes are properly attached to the mitotic spindle

= Activation of APC

42
Q

Importance of M Checkpoint

A

Ensures that daughter cells do not end up with missing or extra chromosomes

(ensures proper chromosomal segregation)

43
Q

An additional checkpoint we know of…

A

Intra-S Phase Checkpoint

44
Q

If the G1 checkpoint is passed prematurely…

A

= Insufficient cell size

–> Daughter cells will be too small to support life

45
Q

If the G2 checkpoint is passed prematurely…

A

= Incomplete chromosome replication

–> Daughter cells will lose genetic info

46
Q

It the M checkpoint is passed prematurely…

A

= Incomplete attachment of chromosomes to microtubules

–> Daughter cells will receive wrong # of chromosomes

47
Q

Cancer cells grow out of control because… (2)

A

1) Don’t respond to normal signals that regulate the cell cycle

2) Lost the ability to survey whether condition of okay or not

48
Q

Rhythmic fluctuations in the _______ and _______ of cell cycle control molecules pace the ________________________________

A

1) Abundance
2) Activity

3) sequential events of the cell cycle

49
Q

Regulatory Molecules of the Cell Cycle

A

1) Protein Kinases (cyclin dependent kinases)
2) Cyclin

50
Q

Protein Kinases

A

Enzymes that catalyze the addition of a phosphate group to a target protein (phosphorylates)

–> Convert ATP to ADP and uses the free Pi group to attach to the target protein

51
Q

Impact of Phosphorylation on Proteins

A

Phosphate is a very negatively charged group which can dramatically change the shape of a protein and therefore, the function of the target protein

52
Q

What molecule is the opposite of a kinase?

A

PHOSPHATASE

–> Dephosphorylates

53
Q

Kinases that drive the cell cycle

A

Cyclin Dependent Kindases (cdks)

54
Q

Cyclin Dependent Kinases (cdks)

A

Kinases that rely on cyclin to activate

55
Q

Cdks are usually ________________ in the cell

A

INACTIVE

–> They must bind to cyclin to activate

56
Q

The concentration of cdks …

A

Remains constant (ALWAYS present in cells)

57
Q

Cyclin

A

A protein that gets its name from its cyclically fluctuating concentration in cells

(Binds to cdks to activate them)

58
Q

The activity of a cdk rises and falls with…

A

changes in the concentration of its cyclin partner

59
Q

Cyclin concentration is…

A

Always changing

–> Cyclin is only made at certain times in the cell cycle

60
Q

Upon binding of cyclin and a cdk, what occurs to the cdk?

A

The active site is exposed, allowing the target protein to bind and phosphorylation to occur

61
Q

G2 Checkpoint cdk complex:

A

MPF = “Maturation (Mitosis) Promoting Factor”

62
Q

MPF

A

“Maturation (Mitosis) Promoting Factor”

63
Q

What was the first cyclin-cdk complex discovered?

A

MPF

64
Q

G2 Checkpoint cdk complex:

As cyclin conc. peaks…

A

MPF activity peaks

65
Q

G2 Checkpoint cdk complex:

Synthesis of cyclin begins when? Why?

A

In LATE S-PHASE –> Synthesis continues through G2

= cyclin accumulation

–> Cannot be made in G1 or M phase as cyclin degradation occurs in these 2 phases

66
Q

How is MPF produced?

A

Cyclin binds to cdk forming the MPF complex

67
Q

When enough MPF molecules accumulate…

A

The cell passes G2 checkpoint and enters mitosis

68
Q

How does MPF promote mitosis?

A

By phosphorylating various proteins

69
Q

What proteins does MPF phosphorylate?

(What is the result of this?)

A

1) Chromosomal proteins –> Initiates chromosomal condensing (In prophase)

2) Microtubule associated proteins –> Activates mitotic spindle
(In prophase)

3) NUCLEAR LAMINS –> Causes disassembly of the nuclear membrane (In Pro-Metaphase)

70
Q

What does MPF do during anaphase?

A

MPF phosphorylates an enzyme that degrades the cyclin component of MPF

–> Causes its own destruction

71
Q

G2 Checkpoint cdk complex:

What is the result of cyclin destruction?

A

MPF deforms which causes M phase to terminate and cell to enter G1 phase

72
Q

What happens to MPF complex in G1?

A

1) Cyclin degradation continues

2) MPF cdk gets recycled for the next cell cycle

73
Q

Internal Signals for Cell Cycle Control

A

Report whether crucial cellular processes that should have been completed have in fact been completed correctly

(Determining cell cycle progression)

74
Q

External Signals for Cell Cycle Control

A

Signals from outside the cell are transmitted within the cell by signal transduction pathways

(Usually have to do with G1 checkpoint –> deciding whether to begin cell division or not)

75
Q

Signal for the M Checkpoint

A

APC

76
Q

Does the M Checkpoint involve external or internal signalling?

A

Internal Signal (APC)

77
Q

What activates APC?

A

A tension-dependent kinase

78
Q

Once APC is activated…

A

it enables SEPARASE to cleave the cohesins between sister chromatids (allowing for anaphase to occur)

79
Q

Wound healing external signalling

A

When an injury occurs, platelets in the area release PDGF, a growth factor that binds to cells with the specific receptor

80
Q

PDGF

A

Platelet-Derived Growth Factor

–> The binding of PDGF to receptors (TK) on the outside of other cells = signal transduction pathway which causes cells to pass the G1 checkpoint and begin division

81
Q

What receptor does PDGF bind to?

A

Tyrosine-Kinase Receptor

82
Q

Transduction pathway due to PDGF result in…

A

An increase in G1 cyclin

83
Q

Process of PDGF Signaling

A

1) PDGF arrives from other cells

2) PDGF binds to TK receptor = triggers cascade

3) Increase in G1 cyclin

4) Cyclins activate cdks

5) Cdks activate many S PHASE PROTEINS (by phosphorylation)

6) Activated S-Phase proteins push cells to division (pass G1 checkpoint)

84
Q

Growth Factor

A

A protein released by certain cells that stimulate other cells to divide

EXTERNAL signals that STIMULATE cell division

85
Q

What are the scientific applications of growth factors?

A

Scientists use growth factors to proliferate cell cultures needed to conduct their studies and experiments

86
Q

Muscle Growth Cell Signaling

A

Muscle cells DO NOT usually divide due to the presence of a growth inhibitor (myostatin)

87
Q

Myostatin

A

A protein that inhibits the growth (division) of myoblasts (fuse with each other to form skeletal muscle cells)

88
Q

What does myostatin do? What is its effect?

A

Acts by CONTINUOUSLY inhibiting the growth of muscles beginning early in embryonic development and continuing through life

–> Works to prevent crazy muscle growth

89
Q

How does myostatin work?

A

Myostating induces the degradation of G1 cyclin –> Causing a blockage in the passage of the cell from G1 to S phase

–> ARRESTS the cell in G1

90
Q

MSTN

A

Myostatin gene

91
Q

What occurs when myostatin is mutated?

A

Can cause excessive growth of muscles in organisms

–> Inhibiting myostatin removes the inhibition of cell division in muscle cells

92
Q

Examples of Myostatin Mutation (2):

A

1) The bully whippet (dog)

2) Belgium blue breed (cattle)

93
Q

What are the implications of inhibiting myostatin?

A

1) Livestock
2) Human Health
3) Athletics

94
Q

How are Myostatin and PDGF OPPOSITES?

A

PDGF = Activates production of G1 cyclin

Myostatin = Triggers degradation of G1 cyclin