Tumour pathology 4

Question 1

Describe the G1 phase

Answer 1

• Cell increases in size

- G1 checkpoint control ensures cell is ready for DNA synthesis

Question 2

Describe the S (interphase) phase

Answer 2

DNA replication occurs

Question 3

Describe the G2 phase

Answer 3

• Cell continues to grow

- G2 checkpoint ensures cell is ready for mitosis

Question 4

Describe M (mitosis) phase

Answer 4

• Cell division

- Metaphase checkpoint ensures cell is ready to complete division

Question 5

Mechanisms of cell cycle control

Answer 5

• Quality control
• Checkpoints
• External factors
• Intrinsic factors

Question 6

Describe quality control

Answer 6

Ensures genetic fidelity in daughter cells

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

Question 7

Describe checkpoints

Answer 7

Monitor and regulate progress

Question 8

Describe external factors

Answer 8

Hormones, growth factors, cytokines

Question 9

Describe intrinsic factors

Answer 9

Critical checkpoints - restriction point

Question 10

Describe the G0 (quiescent) phase

Answer 10

Resting phase; cell has left cycle and stopped dividing

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

Question 11

What checkpoint is used if cell is too small?

Answer 11

G1 and G2

Question 12

What checkpoint is used if nutrient supply is low?

Answer 12

G1

Question 13

What checkpoint is used if external stimulus is lacking/

Answer 13

G1

Question 14

What checkpoint is used if DNA not replicated?

Answer 14

S

Question 15

What checkpoint is used if DNA damage is detected?

Answer 15

G1 and G2

Question 16

What checkpoint is used if there is chromosome misalignment?

Answer 16

M

Question 17

What are cyclin dependent kinases (CDKs)?

Answer 17

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

Different CDKs at each phase

Question 18

What are cyclins?

Answer 18

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

Question 19

What happened when CDKs and cyclins bind?

Answer 19

• Active CDK/cyclin complexes phosphorylate target proteins

- Phosphorylation results in activation/inactivation of that substrate

Question 20

Checkpoint mechanism at G1

Answer 20

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

Question 21

Describe regulation of CDK activity

Answer 21

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

Question 22

What is pRb function?

Answer 22

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

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

Question 23

What is carcinogenesis?

Answer 23

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

Question 24

What does uncontrolled proliferation lead to?

Answer 24

Tumours

Question 25

What gene mutations lead to loss of proliferation control?

Answer 25

Genes regulating cell division, apoptosis and DNA repair

Question 26

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

Answer 26

Purine and pyrimidine

Question 27

What two pathways are frequently disrupted in cancer?

Answer 27

• Cyclin D-pRb-E2F pathway

- p53 pathway

Question 28

p53 function

Answer 28

Levels increase in damaged cells

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

Question 29

p53 in cancer

Answer 29

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

Daughter cells proliferate and form malignant neoplasms