Tumour pathology 4 Flashcards

1
Q

Describe the G1 phase

A
  • Cell increases in size

- G1 checkpoint control ensures cell is ready for DNA synthesis

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2
Q

Describe the S (interphase) phase

A

DNA replication occurs

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3
Q

Describe the G2 phase

A
  • Cell continues to grow

- G2 checkpoint ensures cell is ready for mitosis

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4
Q

Describe M (mitosis) phase

A
  • Cell division

- Metaphase checkpoint ensures cell is ready to complete division

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5
Q

Mechanisms of cell cycle control

A
  • Quality control
  • Checkpoints
  • External factors
  • Intrinsic factors
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6
Q

Describe quality control

A

Ensures genetic fidelity in daughter cells

  • Each cells receives full chromosome complement
  • Mutations in DNA sequences not passed on
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7
Q

Describe checkpoints

A

Monitor and regulate progress

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8
Q

Describe external factors

A

Hormones, growth factors, cytokines

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9
Q

Describe intrinsic factors

A

Critical checkpoints - restriction point

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10
Q

Describe the G0 (quiescent) phase

A

Resting phase; cell has left cycle and stopped dividing

Cells that don’t divide stay in G0 - cardiac and neuronal cells

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11
Q

What checkpoint is used if cell is too small?

A

G1 and G2

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12
Q

What checkpoint is used if nutrient supply is low?

A

G1

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13
Q

What checkpoint is used if external stimulus is lacking/

A

G1

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14
Q

What checkpoint is used if DNA not replicated?

A

S

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15
Q

What checkpoint is used if DNA damage is detected?

A

G1 and G2

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16
Q

What checkpoint is used if there is chromosome misalignment?

A

M

17
Q

What are cyclin dependent kinases (CDKs)?

A

Catalytic subunits that are present in all cells in their inactive form - they act as checkpoint

Different CDKs at each phase

18
Q

What are cyclins?

A
  • Regulatory sub-units that also act as checkpoints
  • Different at each phase
  • They accumulate then are destroyed as cycle progresses
19
Q

What happened when CDKs and cyclins bind?

A
  • Active CDK/cyclin complexes phosphorylate target proteins

- Phosphorylation results in activation/inactivation of that substrate

20
Q

Checkpoint mechanism at G1

A

CDK-4 and cyclin D bind and phosphorylate Rb (inactivating it) which blocks it from inhibiting DNA replication (loses affinity for E2F transcription factor) allowing cell cycle to continue

21
Q

Describe regulation of CDK activity

A
CDK inhibitors (CKIs) like INK4As family which bind to CDK4 and 6 and prevents their cyclin proteins from binding 
-CIP/KIP family 

Without CDK-4 and cyclin D - pRb will bind to E2F and stop the cell cycle

22
Q

What is pRb function?

A

Targets E2F transcription factor - active pRb inactivates E2F which prevents DNA replication (stops cell cycle)

Hypophosphorylated - active
Phosphorylated - inactive (loses affinity for E2F)

23
Q

What is carcinogenesis?

A

Genetic disease caused by a mutation that disrupts the normal balance between proliferation and apoptosis

24
Q

What does uncontrolled proliferation lead to?

A

Tumours

25
Q

What gene mutations lead to loss of proliferation control?

A

Genes regulating cell division, apoptosis and DNA repair

26
Q

What two bases in DNA are damaged by chemical and radiation carcinogens?

A

Purine and pyrimidine

27
Q

What two pathways are frequently disrupted in cancer?

A
  • Cyclin D-pRb-E2F pathway

- p53 pathway

28
Q

p53 function

A

Levels increase in damaged cells

  • Induced cycle arrest at G1
  • Facilitates DNA repair
  • Apoptosis in severe damage
29
Q

p53 in cancer

A

Mutated p53 does not arrest at G1 or repair damaged DNA so daughter cells inherit mutations

Daughter cells proliferate and form malignant neoplasms