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POM 2 Cell biology > 2.8 Cell Replication > Flashcards

2.8 Cell Replication Flashcards

1
Q

What is the cell cycle?

A

An orderly sequence of events in which the cell duplicates its contents and divides in two

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2
Q

What stages of the cell cycle make up interphase?

A

G1 + S + G2

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3
Q

What factors do different rates of mitosis depend on? CENTS

A

Complexity of system
Embryonic vs adult
Need for renewal of cells
Tumour
State of differentiation

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4
Q

Which cells never divide?

A

Neurons, skeletal muscle, hepatocytes

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5
Q

What does pre-mature, abnormal mitosis result in?

A

Cell death

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6
Q

Why is mitosis the most vulnerable period of the cell cycle?

A

DNA damage cannot be repaired, gene transcription is silenced, cell metabolism is low, thus cells are killed more easily

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7
Q

What is G0?

A

The quiescent phase

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8
Q

What state are the cells in when they are in G0?

A

The cells are not dormant, but non-dividing

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9
Q

What does the centrosome consist of?

A

Two centrioles at 90 degrees to one another

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10
Q

What is a centriole?

A

Barrels of 9 triplet microtubules which form the mitotic spindle

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11
Q

Where do the microtubules grow from on the centrosome?

A

Microtubules grow from the nucleating site on the centrosome

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12
Q

Microtubules are polymers of what?

A

Alpha and beta tubulin dimers

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13
Q

What is a kinetochore?

A

Protein complexes that assemble at the centromere of a chromosome and function to connect the chromosome to the microtubules during anaphase

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14
Q

In what phase of mitosis does the spindle attach to the kinetochore?

A

During metaphase

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15
Q

What happens to the microtubules during anaphase?

A

They get shorter as they pull chromosomes apart

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16
Q

In which phase d the spindle microtubules start to form?

A

Prophase

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17
Q

What occurs in the G1 phase of the cell cycle?

A

The cell makes mRNA and proteins in preparation for the next steps

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18
Q

What is aneuploidy?

A

An abnormal number of chromosomes

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19
Q

What is meant by syntelic attachment of the spindle?

A

When both kinetochores attach to spindles from one spindle pole, so the whole chromosome is pulled to one pole

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20
Q

What is meant by merotelic attachment?

A

When spindle fibres from two poles attach to one kinetochore

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21
Q

What occurs during the S phase?

A

Organelle replication and protein synthesis

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22
Q

What happens during the G2 phase?

A

Period of rapid cell growth in preparation for mitosis

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23
Q

What happens to cohesin during anaphase?

A

Cohesin breaks down

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24
Q

What occurs during telophase?

A

The daughter chromosomes arrive at the spindle and nuclear envelopes reassemble at each pore

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25
Q

What happens to chromatin during prophase?

A

Chromatin condenses

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26
Q

What is the function of a microtubule organising centre?

A

Forms the spindle fibers

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27
Q

How do we get cell growth? (Leaving G0 to G1)

A

Growth factors bind tyrosine kinase receptors in cell surface (mitogen signalling)

This triggers an intracellular signalling pathway, increasing protein synthesis and decreasing degradation, stimulating cell growth

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28
Q

What type of molecule is c-Myc?

A

A transcription factor and oncogene which is overexpressed in many tumours

29
Q

What does c-Myc promote?

A

G0 to G1 transition

30
Q

Which oncogene is over expressed in many tumours?

A

c-Myc

31
Q

What two things can occur if something goes wrong with cell replication?

A
  1. Cell cycle arrest while DNA damage is being fixed
  2. Apoptosis (programmed cell death)
32
Q

In the absence of a stimuli to progress into the next stage of replication, what happens to the cell?

A

Cells go into G0 phase (quiscent phase)

33
Q

What does the exit from G0 phase require?

A

Growth factors and intracellular signalling cascades

34
Q

What forms when cyclins bind to cyclin dependant kinases?

A

They form an activated cyclin-CDK complex

35
Q

What do cyclin dependant kinases have to bind to in order to be activated?

A

Cyclins

36
Q

Which Cyclin-Cdk complex leads to the progression into G1 phase?

A

Cyclin D - Cdk4/6 complex

37
Q

Which Cyclin-Cdk complex leads to the progression into S phase?

A

Cyclin E - Cdk2 complex

38
Q

Which Cyclin-Cdk complex leads to the progression into M phase?

A

Cyclin A - Cdk2 complex

39
Q

Which Cyclin-Cdk complex is formed after M phase?

A

Cyclin B - Cdk1 complex

40
Q

How are cyclins expressed through the cell cycle?

A

Transiently

41
Q

How are cyclins switched off during the cell cycle?

A

They are made inactive by ubiquitylation - where ubiquitin molecules are added so the cell degrades the cyclin, thus inactivating the Cdk

42
Q

What is retinoblastoma?

A

A tumour suppressor

43
Q

How does retinoblastoma protein work?

A

Active Rb holds an inactive E2F transcription factor (that cannot turn on genes for cell cycle progression) and only releases it when Rb is phosphorylated

44
Q

What phosphorylates Rb?

A

Activated cdk-cyclin complexes

45
Q

What does mitogen signalling do to Rb, in a proliferating cell?

A

Mitogens activate intracellular signalling, leading to G1-Cdk and G1/S-Cdk complex production

The complexes phosphorylate the active Rb bound to E2F, inactivating Rb and releasing E2F

46
Q

What does phosphorylation of Rb lead to?

A

Target genes needed for cell cycle progression (e.g. DNA polymerase, thymidine kinase) can now be activated

47
Q

Describe how p53 works as a tumour suppressor?

A

p53 recognises damage to DNA

p53 is phosphorylated and activated

Activated p53 binds to p21 gene, activating transcription and translation

The p21 enzyme inhibits cyclin-cdk complexes, preventing phosphorylation of Rb thus the cell cycle cannot progress

48
Q

What does p21 do?

A

Inhibits cdk-cyclin complex formation, preventing the phosphorylation of Rb

49
Q

When does Cdk activity peak?

A

During mitosis

50
Q

What does c-Myc induce the expression of?

A

Cyclin D

51
Q

Why is cyclin D so important?

A

Entry to the cell cycle requires Cyclin D

52
Q

What two checkpoints can occur in the G1 phase?

A

Check for damaged DNA
Check for unfavourable extracellular environments

53
Q

What checkpoints can occur in the S and G2 phase?

A

Check for damaged or incompletely replicated DNA

54
Q

Why are checkpoints needed in the cell cycle?

A

The cell can pause at checkpoints to repair DNA or undergo apoptosis if DNA is unrepairable

This prevents passing on of damaged DNA to progeny, preventing cancer

55
Q

What can induce a checkpoint in mitosis?

A

Check for chromosomes improperly attached to the mitotic spindle

56
Q

What do protein kinase cascades lead to and why?

A

Signal amplification, diversification and an opportunity for regulation

Since the activity of kinases is regulated by phosphorylation (by other kinases) and dephosphorylation (by phosphatases)

57
Q

Why are protein kinases useful for cell cycles?

A

Since the protein kinases can be turned on and off, it is very helpful in regulating the progression through the cell cycle

58
Q

What actually activates Cdks?

A

When the cyclin binds to Cdk, the complex is still inactive

The complex has to be phosphorylated with both inhibitory and activating phosphates

Once the inhibitory phosphate is removed by protein phosphatase, the complex is activated

59
Q

What removes inhibitory phosphates from the Cdk complexes in order to make it active?

A

Phosphatase

60
Q

How does positive feedback in the Cdk-cyclin system work?

A

The active Cdk complexes then activate more phosphatases so more inhibitory phosphates can be removed from the inactive complexes, leading to more activation of complexes

61
Q

During ubiquitination, what do cyclins get degraded into?

A

Amino acids

62
Q

How might over expression of c-Myc lead to aberrant cell cycling and cancer?

A

Inappropriate entry into G1 – S phase

63
Q

How are Cdks rendered active to allow progression to the next phase of the cell cycle?

A
  1. Binding of cyclins
  2. Phosphorylation
  3. Dephosphorylation
64
Q

How are active Cdk-cyclin complexes rendered inactive to allow orderly progression to the next phase of the cell cycle?

A

Degradation of cyclins

65
Q

How can p53 rapidly respond to DNA damage?

A

p53 protein is continuously made and degraded

66
Q

What oncogenes are mutationally activated or over expressed in breast cancers?

A

EGFR/HER2
Cyclin D1

67
Q

How does herceptin antibody treat HER2+ metastatic breast cancer?

A

It blocks HER2 signalling and stops uncontrolled cell proliferation

68
Q

What tumour suppressors are relevant in the cell cycle?

A

Rb – loss of function mutations in 80% of small cell lung cancers
p53 – loss of function mutations in 50% of all cancers

POM 2 Cell biology (15 decks)

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