Cell Cycle and its Regulation Flashcards

1
Q

Which human cells divide the most?

A

Embryonic

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2
Q

What process do cells normally use to grow? (to grow in one direction and not the other, tumours lack this)

A

Contact inhibition of growth

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3
Q

What is the most vulnerable point of the cell cycle? Why

A

Mitosis, cells are more easily killed during this phase.

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4
Q

What happens to gene transcription during mitosis

A

It is completely silenced

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5
Q

What happens to metabolism during mitosis

A

Slows down

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6
Q

If you damage DNA during mitosis what can you do

A

Nothing, it can’t be repaired

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7
Q

When is DNA damage irreparable

A

During mitosis

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8
Q

What are the 2 major phases of the cell cycle

A

M phase and interphase

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9
Q

What is interphase divided into

A

G0 G1 S G2

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10
Q

What is G0

A

Cell cycle machinery disabled, the cell is just resting

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11
Q

What does the cell do during G1

A

The cell considers if its necessary to divide

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12
Q

Which is the quickest part of the cell cycle and why

A

Mitosis because the cell is so vulnerable

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13
Q

What is the main thing that happens during S phase

A

Synthesis of protein, DNA replication, organelle replication

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14
Q

What does the cell do during G2

A

The cell checks everything is okay and that everything has been doubled and is ready to go into mitosis

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15
Q

What does centrosome consist of

A

2 centrioles

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16
Q

What is a centriole made of

A

Barrels of 9 triplet microtubules

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17
Q

What are the two main functions of a centriole

A

The microtubule organising centre (MTOC) and the mitotic spindle

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18
Q

What is the centrosome

A

An organelle near the nucleus of a cell which contains the centrioles, and from which the spindle fibres develop in cell division

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19
Q

What are the two centrioles referred to as, which one is which (think of their arrangement)

A

The mother and daughter, mother is the top of the T

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20
Q

What do the centrioles orchestrate

A

The microtubule network to orchestrate cell division

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21
Q

What are the nucleating sites of the centrosomes made of

A

Gamma-tubulin ring complexes

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22
Q

What needs to happen to the centrosome/centrioles for mitosis to occur

A

They need to duplicate

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23
Q

What happens in G1 to the centrosome

A

Separation of the mother and daughter centrioles

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24
Q

What happens after the mother and daughter centrioles separate and what phase does this occur during

A

They start to duplicate, the mother produces a daughter and vice versa, during S

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25
Q

What is nucleation

A

Putting microtubules together

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26
Q

Where are nucleating sites found (regarding centrioles)

A

In a cloud of protein complexes around the centrioles

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27
Q

Where do microtubules grow from

A

The nucleating points in the cloud of protein around the centrioles

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28
Q

What are the 6 phases of the cell cycle

A

Interphase, prophase, metaphase, anaphase, telophase, cytokinesis

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29
Q

What happens to DNA during prophase? Why? What is used to condense it

A

They condense to minimise DNA damage, histone proteins are used to wrap the DNA around

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30
Q

Describe how DNA is condensed

A

Short region of DNA double helix to beads on a string form of chromatin, to 30nm chromatin fibre of packed nucleosomes to an extended scaffold associated form to condensed scaffold associated form to condensed chromosomes

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31
Q

What difference to width of the chromosome from the with of a DNA double helix does condensation result in

A

2nm to 300nm which is wrapped to maker a super wide chromosome

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32
Q

What is the kinetichore fundamentally (molecule type and where)

A

Protein complexes that form at the centromere

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33
Q

What is the function of the kinetochore

A

To be a key regulator of processes around the chromosomes in the cell cycle

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34
Q

What are the 3 key events of prophase

A

Duplicated centrosomes migrate to opposite poles of the nucleus and replicated chromosomes condense and nuclear envelope begins to break down

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35
Q

By what point are there two centrosomes

A

Late prophase

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36
Q

What begins at the start of late prophase

A

The nuclear envelope breaks down

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37
Q

When does the nuclear envelope begin breaking down

A

Late prophase

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38
Q

What happens as the nuclear envelope breaks down

A

Centrosomes migrate to opposite sides of the cell

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39
Q

At what point do centrosomes migrate to opposite ends of the cells

A

Late prophase

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40
Q

What do the centrosomes begin to do when they reach opposite sides of the cell

A

Organise the spindle

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41
Q

What are ASTERS

A

Radial microtubule arrays

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42
Q

What are radial microtubule arrays also knows as

A

ASTERS

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43
Q

What do radial microtubule arrays/ASTERS form around

A

MTOC (microtubule organising centre)

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44
Q

When do radial arrays/ASTERS begin to form

A

Late prophase

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45
Q

What are radial arrays/ASTERS called when they join spindle fibres

A

Polar microtubules

46
Q

Are microtubules/spindle fibres static structures

A

No, they are constantly polymerising and depolymerising and being turned over

47
Q

What happens during early prometaphase (3)

A

Breakdown of nuclear membrane
Spindle formation
Attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)

48
Q

Where on the chromosome do spindle fibres attach

A

The kinetochores

49
Q

What happens during late prometaphase (3)

A

Microtubule from opposite pole is captured by its sister kinetochore
Chromosomes attached to each pole congress to the middle
Chromosome slides rapidly towards centre along microtubules for alignment to occur

50
Q

What 2 proteins in the kinetochore senses the attachment of microtubules

A

CENP-E

BUB protein kinase

51
Q

What is CENP-E and its function

A

A protein in the kinetochore which senses the attachment of microtubules

52
Q

What are the three types of half spindle and where do they bind

A

Kinetochore microtubule - bound to the kinetochore
Polar microtubule - A microtubule that has met and connected with a microtubule from the other centrosome
Astral microtubule - microtubule that is originating from the centrosome that does not connect to a kinetochore

53
Q

What holds sister chromatids together

A

Cohesin

54
Q

When do paired chromatids separate

A

During anaphase

55
Q

What happens during anaphase A (3)

A

Cohesin breaks down
Microtubules get shorter
Daughter chromosomes pulled towards opposite spindle poles

56
Q

When does cohesin break down

A

Anaphase A

57
Q

What happens during anaphase B (2)

A
Daughter chromosomes migrate towards poles by the spindle fibres breaking down and becoming shorter
Spindle poles (centrosomes) migrate apart
58
Q

What happens during telophase

A

Daughter chromosomes arrive at each pole
Nuclear envelope reassembles at each pole
Cells try to revert to their normal size

59
Q

What is a contractile ring made of

A

Actin and myosin

60
Q

How does the cell cleave into two

A

The contractile ring squeezes the cell so that it divides into two daughter cells

61
Q

What is a cleavage furrow

A

Where two cells are going to be cleaved during cytokinesis

62
Q

What is the midbody of cytokinesis

A

Where the actin myosin contractile ring forms

63
Q

When is the spindle assembly checkpoint/mitotic checkpoint

A

When the cell wants to exit metaphase and enter anaphase (a.k.a. the anaphase checkpoint)

64
Q

What inhibits CENP-E from making a signal

A

Microtubule attachment

65
Q

What protein dissociates from the kinetochore when chromatids are properly attached

A

BUB protein kinase

66
Q

What is the function of BUB protein kinase

A

To dissociate from the kinetochore when microtubules attach to the kinetochore, this then signals the cell to tell it to proceed into anaphase

67
Q

How can you get aneuploidy

A

If anaphase initiates before the spindle fibres attach/attach properly

68
Q

What are the four types of misattachment of microtubules called

A

Syntelic, amphelic, monotelic and merotelic

69
Q

What is syntelic attachment

A

Both kinetochores are hooked from microtubule arrays from the same centrosome

70
Q

What is amphelic attachment

A

Normal microtubule attachment to the kinetochore

71
Q

What is merotelic attachment

A

When there is more than one microtubule array attached to the same kinetochore -­‐ this means that one of the chromatids is being pulled in two different directions

72
Q

What is monotelic attachment

A

When only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached

73
Q

What is normal microtubule attachment to the kinetochore known as

A

Amphelic attachment

74
Q

What is it called when only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached

A

Monotelic attachment

75
Q

What is it called when more than one microtubule array attached to the same kinetochore - meaning that one of the chromatids is being pulled in two different directions

A

Merotelic attachment

76
Q

What is it called when both the kinetochores are hooked by two microtubule arrays from the SAME centrosome

A

Syntelic attachment

77
Q

What does merotelic attachment result in

A

Loss of the chromosome at cytokinesis

78
Q

What does syntelic attachment and monotelic attachment result in

A

Both sister chromatids at the same pole

79
Q

What type of microtubule attachment results in a loss of a chromatid at cytokinesis

A

Merotelic

80
Q

What are the three roads to aneuploidy

A

Mitotic checkpoint defect
Misattachment of microtubules to kinetochores
Aberrant cytokinesis

81
Q

How can you get aberrant mitosis (think of centromere duplication)

A

Centromeres that aren’t duplicated properly could mean you have 4 centrosomes in one cell, or 1 centrosome doesn’t form a spindle properly or something so you end up with more chromatids in one cell and none in another

82
Q

What can exploiting checkpoint control mechanisms achieve

A

Inhibition of the proliferation of a tumour

83
Q

What holds cells in G2 until all is ready to proceed into mitosis

A

CHKE1 and CHKE2 (serine threonine kinase)

84
Q

What do taxanes and vinca alkaloids do (3) and what cancers are they used for (2)

A

Alter microtubule dynamics
Produces unattached kinetochores
Causes long-term mitotic arrest
Breast and ovarian

85
Q

What does CENP-E inhibition do

A

Cause the cell to think it has correctly hooked onto microtubules and proceed into anaphase

86
Q

What happens if something goes wrong during the cell cycle? (2)

A

Cell cycle arrest at checkpoints to try fix problem

Apoptosis if problémo is too big

87
Q

What stimulates cell division

A

Growth factors

88
Q

When is the first cell checkpoint

A

G1

89
Q

What can tumours do to the G1 checkpoint

A

Hijack it and stimulate excessive cell division

90
Q

How many cell cycle checkpoints do we need to know of and where are they

A

3, near the end of G1, just before mitosis and the anaphase/mitotic/spindle assembly checkpoint between metaphase and anaphase

91
Q

What can tumours do to the second checkpoint

A

Block the sensing of DNA damage and cause the cell to continue with mitosis

92
Q

What is the purpose of the second checkpoint

A

To check for DNA damage before entering mitosis

93
Q

What is the third checkpoint and what does it do

A

The metaphase/anaphase checkpoint and it checks that microtubules are attached to kinetochores correctly

94
Q

What do tumours do to the third checkpoint

A

Completely bypass the metaphase/anaphase checkpoint (a.k.a. the mitosis/spindle assembly checkpoint)

95
Q

What can tumours block the ability of a cell to do regarding G0

A

Tumours block the ability of the cell cycle to enter G0, go straight from cell cycle to cell cycle

96
Q

What does a cell need to leave G0

A

Growth factors triggering intracellular signalling cascades

97
Q

What triggers a signalling cascade

A

Extracellular factors binding to receptors and activating them

98
Q

What happens to the signal generated by a signalling cascade as it travels

A

It is relayed, amplified and integrated and then is diverted to multiple targets

99
Q

Give two examples of peptide growth factors

A

Epidermal growth factor (EGF) and platelet derived growth factor (PDGF)

100
Q

Explain growth factor ligand receptor binding, state of receptor included

A

Receptors are usually found in the monomeric, inactive state.
When a ligand binds to the EC domain of the monomeric receptor, the receptors come closer and form dimers by activating the kinase domain. The kinase domain phosphorylates one another to activate the receptor.

101
Q

What are growth factor receptors known as

A

Receptor protein tyrosine kinase

102
Q

What type of protein mediates amino acid acid phosphorylation

A

Kinases

103
Q

What is the ‘activation trigger’

A

Phosphorylation of a protein

104
Q

How can phosphorylation of a protein be reversed

A

Protein phosphatases

105
Q

What are the two types of protein kinase

A

Serine and tyrosine

106
Q

What are the three amino acids that can be phosphorylated

A

Serine, threonine and tyrosine

107
Q

Which type of kinase can phosphorylate 2 amino acids and which 2 amino acids?

A

Serine kinase - serine and threonine

108
Q

What charge is on a phosphate group

A

-ve

109
Q

How can a phosphate group alter protein function (2)

A

Cause a change in shape (conformation)

Creating a docking site for another protein

110
Q

What does growth factor receptor activation and dimerisation trigger (2)

A

Kinase cascades

Binding of adaptor proteins

111
Q

What protein does a kinase often regulate? What does this allow (3) and what is the benefit of this?

A

Another kinase. Signal amplification, diversification and opportunity for regulation. Multiple steps allows more control and to fix mistakes

112
Q

What reverses phosphorylation

A

Phosphatases