Tumour Pathology 4

Question 1

What are the 2 main stages of the cell cycle?

Answer 1

Interphase

M phase

Question 2

What are the 5 phases of cell cycle? (In order)

Answer 2

G1 
DNA replication (S phase)
G2 
Mitosis 
Cytokinesis

Question 3

What is the purpose of each stage of the cell cycle?

Answer 3

G1- All the cellular contents except from chromosomes are replicated
S- DNA replication/synthesis
G2- Double-checking of any chromosomal errors and repair if any are present
Mitosis - Division of genetic material within 2 nuclei in the same cell
Cytokinesis - Production of two daughter cells, each with one nucleus, through separation of cytoplasm.

Question 4

How is the sequence of the cell cycle controlled?

Answer 4

Checkpoints
Activators
Breaks

Question 5

What is the G1/S restriction point?

Answer 5

Cells that pass this point are committed to go through the S phase
Before the S point cells in cell cycle are controlled by external factors
After S point cells in cell cycle are autonomously controlled

Question 6

What are the different points in the cell cycle at which there could be an arrest?

Answer 6

G1 to S phase / S
G2 to M phase / G2
G1
M

Question 7

What controls the different phase arrest?

Answer 7

Checkpoints

Question 8

Why would there be an arrest in S/G1 to S phase?

Answer 8

Unreplicated DNA

Question 9

Why would there be an arrest in G2/G2 to M phase?

Answer 9

Unreplicated or damaged DNA

Question 10

Why would there be an arrest in the M phase?

Answer 10

DNA misalignment/ deletion or tandem repeats

Question 11

Why would there be an arrest in the G1 phase

Answer 11

Damaged DNA or inadequate nutrients

Question 12

What are activators?

Answer 12

Active or inactive enzymes that act as switches in the cell cycle

Question 13

What are activators composed of ?

Answer 13

cyclin and cyclin dependent kinase

Question 14

Which is the regulatory component of activators?

Answer 14

cyclin

Question 15

How do CDK/cyclin complexes work?

Answer 15

They operate in sequential stages
When cyclin -CDK complexes are active they phosphorylate target proteins.
Target proteins then become active or inactive and pass on to regulate the next phase of the cell cycle.

Question 16

How does S phase preparation occur?

Answer 16

The G1 Cyclin/CDK complex become active

Question 17

What is an example of pro-mitotic signals?

Answer 17

G1 Cyclin-CDK complexes

Question 18

What is required for DNA replication?

Answer 18

enzymes and S cyclin

Question 19

How is S cyclin expression promoted?

Answer 19

Through G1 cyclin-CDK complex that becomes active and causes the cell to enter the S phase.

Question 20

What are family examples of CDK inhibitors?

Answer 20

• INK4a

- CIP/KIP

Question 21

What are two examples of an INK4a inhibitors and what is its effect?

Answer 21

p161INK4a inhibitor that binds to CDK4 and stops cell cycle at G1
p14 which inhibits p53 degradation

Question 22

What are examples of CIP/KIP family inhibitors and what is their effect on the cell cycle?

Answer 22

p21
p27
p57
They bind to cyclin-CDK complexes and inactivate them causing cell cycle to stop at G1

Question 23

How is p21 activated?

Answer 23

By p53

Question 24

What is a powerful signal for cell cycle activation?

Answer 24

E2F

Question 25

What is an example of a break in the cell cycle?

Answer 25

Retinoblastoma

Question 26

How is retinoblastoma activated?

Answer 26

Through its hyperphosphorylation by the cyclin/CDK complex

Question 27

How else is Retinoblastoma written?

Answer 27

pRB

Question 28

Why can retinoblastoma act as a break for the cell cycle?

Answer 28

It is a tumour suppressor gene

Question 29

How does retinoblastoma affect the cell cycle?

Answer 29

It carries out its tumour suppressor role causing the cell cycle to stop at G1 phase.

Question 30

Why does inactivation of retinoblastoma inhibit cell cycle from progressing?

Answer 30

pRB loses its affinity to E2F transcription factor, which is a major signal for cell cycle activation

Question 31

What is Carcinogenesis?

Answer 31

Failure of cell cycle control?

Question 32

How is Carcinogenesis caused?

Answer 32

- Inbalance of proliferation and cell apoptosis | - More than one mutations in genes regulating cell division, apoptosis and DNA repair.

Question 33

What are frequently disrupted pathways ?

Answer 33

p53 pathway | cyclin D - pRB - E2F

Question 34

How do malignant neoplasms come about?

Answer 34

Mutant p53 activation, where DNA damage does not cause cell cycle to stop or DNA repair to take place thus leading to proliferation of cells with damaged DNA

Question 35

How is cell repair accomplished?

Answer 35

activation of normal p53 which activates p21 which in turn inactivates cyclin-CDK complex and halts cell cycle at G1 at which stage DNA repair occurs

Question 36

Where are all cancer cells dysregulated?

Answer 36

G1-S phase

Question 37

What genes are most often mutated?

Answer 37

Cyclin D, CDK4, p16, pRB