Cell Proliferation

Question 1

What does cell cycle control involve?

Answer 1

Checkpoints and feedback.

Question 2

List the 4 phases of the cell cycle.

Answer 2

1 - G1.

2 - Synthesis.

3 - G2.

4 - Mitosis

Question 3

What occurs during the G1 phase?

Answer 3

• Growth.

- Preparation for DNA replication (synthesis phase).

Question 4

What occurs during the G2 phase?

Answer 4

Growth only.

Question 5

Which of the phases of the cell cycle are known as interphase?

Answer 5

• G1.
• S.
• G2.

Question 6

What are checkpoints?

Answer 6

Control points in the cell cycle where stop and go-ahead signals regulate the cycle.

Question 7

List the checkpoints of the cell cycle.

Answer 7

• The G1 / S checkpoint.
• The G2 / M checkpoint.
• The metaphase checkpoint.

Question 8

What does the G1 / S checkpoint check?

Answer 8

1 - That the cell is large enough to divide.

2 - That enough nutrients are available to support the daughter cells.

3 - That there is no DNA damage.

Question 9

What is G0 / quinescence?

Answer 9

A non-dividing state (most of the cells of the body are in this state).

Question 10

What does the G2 / M checkpoint check?

Answer 10

That DNA replication in S phase has been completed successfully.

Question 11

What does the metaphase / anaphase checkpoint check?

Answer 11

That all of the chromosomes are attached to the mitotic spindle by a kinetochore.

Question 12

Which molecules regulate cell cycle checkpoint transitions?

Answer 12

• Cyclin-dependent kinases.

- There is a different Cdk for each checkpoint.

Question 13

What activates cyclin-dependent kinases?

Answer 13

Cyclin.

Question 14

What is M-Cdk known as?

Answer 14

Maturation promoting factor.

Question 15

How do cyclin-dependent kinases bring about their actions?

Answer 15

By phosphorylation.

Question 16

How do cyclins switch themselves off?

Answer 16

By initiating a process which leads to the destruction of cyclin.

Question 17

When are cyclin-dependent kinases expressed?

Answer 17

• Continuously.

- They persist in the cell either in an inactive form or in an active form

Question 18

What ensures that all cyclin-dependent kinases aren’t activated at once?

Answer 18

Each checkpoint requires different cyclin-dependent kinases, which only form when there is enough of the cyclin-dependent kinases needed to surpass the previous checkpoint.

Question 19

List the cyclin-dependent kinases that are required to surpass each stage of the cell cycle.

Answer 19

• Restriction point: Cdk4 and cdk2.
• G1 / S checkpoint: Cdk2 and cdk1.
• G2 / M checkpoint: Cdk1.

Question 20

What is the restriction point?

Answer 20

• A checkpoint during the G1 phase.

- The means by which cells enter the G0 phase.

Question 21

List the cyclins that are required to activate each cyclin-dependent kinase.

Answer 21

• Cdk 1: Cyclin A/B.
• Cdk 2: Cyclin E/A.
• Cdk4: Cyclin D.

Question 22

How do cyclins activate cyclin-dependent kinases?

Answer 22

By phosphorylation.

Question 23

What is INK?

Answer 23

A molecule that inhibits cdk4.

Question 24

What are CIP / KIP?

Answer 24

Molecules that inhibit a broad spectrum of cdks.

Question 25

What is retinoblastoma protein (pRB)?

Answer 25

A regulator of the restriction point, and as such, a tumour suppressor protein.

Question 26

How does retinoblastoma protein (pRB) regulate the restriction point?

Answer 26

In the absence of growth factors, pRB binds to transcription regulators for cell proliferation, preventing continuation of the cell cycle.

Question 27

How do growth factors prevent the action of pRB?

Answer 27

• Growth factors target surface receptors, activating a range of cdks through cyclins.
• G1 / S cdk phosphorylates pRB.

Question 28

What is p53?

Answer 28

A regulator of the G1 / S checkpoint, and as such, a tumour suppressor protein.

Question 29

How does p53 regulate the G1 / S checkpoint?

Answer 29

• DNA damage causes an increase in p53.
• p53 activates the transcription of p21 (a tumour suppressor protein).
• P21 is an inhibitor of cdk, which is necessary for continuation into S phase.

Question 30

How do varying degrees of DNA damage change the effect of p53?

Answer 30

• If DNA damage is too severe, p53 induces apoptosis.
• If DNA damage is not too severe, then the activation of p21 (and the subsequent inhibition of cdk) will give more time for DNA repair.

Question 31

List 4 consequences of checkpoint failure.

Answer 31

1 - Proliferation of cells in the absence of growth factors.

2 - Replication of damaged DNA.

3 - Segregation of incompletely replicated chromosomes.

4 - Division of cells with the wrong number of chromosomes.

Question 32

List 3 ways by which the regulation of cell proliferation can be disturbed.

Answer 32

1 - Receptors that stimulate the expression of growth factors can be mutated - e.g. Her2.

2 - Signalling proteins that stimulate the expression of growth factors can be mutated - e.g. Ras.

3 - Mutated transcription factors that regulate the expression of growth factors. - e.g. myc.