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1.1 POM Cells > Cell Replication > Flashcards

Cell Replication Flashcards

1
Q

What are the 3 main parts of the cell cycle?

A
  1. Cell growth and chromosome replication (size doubles) —> G1, S, G2 (interphase)
  2. Chromosome separation —> M
  3. Cell division —> cytokinesis
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2
Q

How often to hepatocytes divide?

A

Every year

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3
Q

How often to intestinal epithelial divide?

A

Every 20 hours

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4
Q

Which 2 cells never divide?

A
  1. Neurones
  2. Cardiomyocytes
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5
Q

What are the 5 phases of the cell cycle in order?

A
  1. G0
  2. G1
  3. S
  4. G2
  5. M
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6
Q

What is the G0 phase?

A

Quiescent phase —> cell not dividing

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7
Q

What is cytokinesis and when does it occur?

A
  • Cytoplasm dividing
  • Between M and G1
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8
Q

When are cells in G0?

A

No stimulus to divide —> not dormant but not dividing

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9
Q

What is required in the external environment for the cell cycle to stay stable?

A
  • Correct nutrients (proteins, DNA bases, amino acids)
  • Growth factors
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10
Q

What are the 4 stages of signalling cascades stimulating cells to leave G0?

A
  1. Response to extracellular factor (eg. growth factor)
  2. Signal amplification
  3. Signal integration/modulation
  4. Ras/Raf/MEK/ERk (kinases) phosphorylate
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11
Q

What happens if an issue is detected at a checkpoint? (2)

A
  • DNA repair
  • Apoptosis if unfixable
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12
Q

Which transcription factor is expressed to move a cell from G0 to S?

A

c-Myc

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13
Q

What is seen regarding c-Myc in tumours?

A

Over-expressed —> c-Myc gene becomes oncogene

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14
Q

Which enzymes drive a cell through the cell cycle?

A

Cyclin-dependant kinases (Cdks)

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15
Q

Which cells are Cdks present in?

A

Proliferating cells

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16
Q

When are Cdks active? (2)

A
  1. Cyclin is bound
  2. Phosphorylated correctly
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17
Q

Which 3 amino acids allow Cdks to be phosphorylated and why?

A
  1. Serine
  2. Threonine
  3. Tyrosine
    All have hydroxyl group so can undergo phosphorylation
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18
Q

What is important about cyclins? (in name)

A

Produced and degraded in a cycle

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19
Q

Which specific Cdk-cyclin complex is required for a cell to enter the cell cycle?

A

Cdk 4/6-cyclin D

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20
Q

What are the 4 stages required for a cell to leave G0 and enter S?

A
  1. Growth factor stimulates…
  2. C-Myc (TF) production which stimulates…
  3. Cyclin D production which is part of…
  4. Cdk 4/6-cyclin D
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21
Q

What are the 5 key checkpoints in the cell cycle?

A
  1. G1 middle
  2. G1 end
  3. S end
  4. G2 middle
  5. M end
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22
Q

What is the 1st G1 checkpoint checking?

A

No DNA damage

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23
Q

What is the 2nd G1 checkpoint checking?

A

Extracellular environment

24
Q

What is the S checkpoint checking?

A

No DNA damaged/poorly replicated

25
Q

What is the G2 checkpoint checking?

A

No DNA damaged/poorly replicated

26
Q

What is the M checkpoint checking?

A

Chromosome properly attached to mitotic spindle

27
Q

How do protein kinase cascades work?

A

Activated kinase stimulates next kinase to activate

28
Q

How is phosphorylation reversed?

A

Phosphatases

29
Q

Why are signalling cascades important for the cell cycle? (3)

A
  1. Signal amplification
  2. Diversification
  3. Regulation
30
Q

What are the 4 important Cdks for the cell cycle?

A

1, 2, 4, 6

31
Q

What are the 4 important cyclins for the cell cycle?

A

A, B, D, E

32
Q

What are the 3 steps of Cdk activation?

A
  1. Cyclin binds to Cdk —> Cdk-cyclin complex
  2. Phosphorylation —> inhibitory and activating phosphate groups added to Cdk-cyclin complex by protein kinases
  3. Dephosphorylation —> inhibitory phosphate group removed by activating protein phosphatase
33
Q

Why does Cdk activation continue? (2)

A

Positive feedback
1. Active Cdk-cyclin inhibits Cdk-inhibitory kinase —> dec addition of inhibitory phosphate group
2. Active Cdk-cyclin activates more phosphatase via phosphorylation —> inc removal of inhibitory phosphate groups

34
Q

When are Cdk-cyclin S complexes active?

A

S + G2

35
Q

When are Cdk-cyclin M complexes active?

A

M

36
Q

How are cyclins turned off?

A

Ubiquitination

37
Q

What are the 2 steps of cyclin ubiquination

A
  1. Ubiquitin protein attaches to cyclin of active Cdk-cyclin —> marks cyclin for proteasome
  2. Proteasome binds cyclin —> cyclin destroyed —> Cdk inactive
38
Q

How are Cdks activated unidirectionally and at the right time?

A

Active Cdk-cyclin stimulates expression of gene producing next cyclin —> activates next Cdk

39
Q

What are the 4 Cdk-cyclin complexes activated throughout the cell cycle and when are they active?

A
  1. Cdk4/6-cyclin D —> end of G1
  2. Cdk2-cyclin E —> G1 to S
  3. Cdk2-cyclin A —> S to M (metaphase)
  4. Cdk1-cyclin B —> M (prophase to metaphase)
40
Q

What is a retinoblastoma?

A

An eye cancer primarily affecting children

41
Q

What causes a retinoblastoma?

A

Tumour suppressor protein Rb missing/inactive

42
Q

Where is Rb found and why?

A

In all nucleated cells
- controls exit and entry to cell cycle

43
Q

What is the function of mitogen?

A

Growth factor
- Drives protein synthesis
- Inhibits protein degradation

44
Q

What is the function of Rb and how does it do this?

A

Stops cell proliferation
- Active Rb sequesters E2F transcription factors in inactive state —> genes for cell cycle progression not turned on

45
Q

How can Rb be inactivated and which Cdk-cyclin complexes do this?

A

Phosphorylation
- G1-Cdk and G1/S-Cdk

46
Q

What happens when Rb is phosphorylated?

A
  • Inactivated —> transcription factors released —> cell cycle genes activated (DNA polymerase and thymidine kinase)
47
Q

What are E2F family members and what do they do in the cell cycle?

A

Group of transcription factors
- Stimulate expression of genes producing cyclins

48
Q

Which protein prevents cells with damaged DNA leaving G1?

A

p53

49
Q

What is p53?

A

Tumour suppressor protein —> controls cell entry to S phase

50
Q

What does activate p53 stimulate the production of and how?

A

p21
- binds to regulatory region of p21 gene

51
Q

How does p53 prevent cells with damaged DNA leaving G1? (4)

A
  1. Damaged DNA activates protein kinase
  2. p53 phosphorylated by protein kinase —> activated
  3. p53 binds to regulatory region of p21 gene —> p21 produced
  4. p21 binds to Cdk-cyclin complex —> inactivated —> cell can’t progress through cycle
52
Q

What is p21?

A

Cdk inhibitor protein

53
Q

Which 4 proteins from oncogenes are over-expressed in breast cancer?

A
  1. EGFR/HER2
  2. Ras
  3. Cyclin D1
  4. C-Myc
54
Q

What is the treatment for HER2+ metastatic breast cancer?

A

Herceptin antibody

55
Q

Which tumour suppressor proteins cause small cell lung cancers when mutated?

A

Rb (80%)

56
Q

Why is understanding p53 function so important in oncology?

A

Mutations cause most cancers

1.1 POM Cells (15 decks)

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