Cell Cycle Control and Cancer

Question 1

What are the phases of the cell cycle?

Answer 1

M -> G1 -> S -> G2

Question 2

What happens in G1?

Answer 2

Preparation for DNA replication

Question 3

What happens in S phase?

Answer 3

DNA replication

Question 4

What happens in G2?

Answer 4

Preparation for mitosis

Question 5

Describe the chromosomes in each stage of the cell cycle

Answer 5

• In G1, 2N (diploid)
• In S, replication, so 2N -> 4N
• In G2, 4N (tetraploid)
• In mitosis, 4N -> 2N

Question 6

Describe the transitions between phases in the cell cycle?

Answer 6

They occur in an orderly fashion

Question 7

What are the key regulators of the transitions between different stages in the cell cycle?

Answer 7

Cyclin dependant kinases (CDKs)

Question 8

What are CDKs?

Answer 8

Seronine/theonine kinases

Question 9

What do serine/theonine kinases do?

Answer 9

Phosphorylate substrates at SER/THR-PRO-X-LYS/ARG motifs

Question 10

What do the CDK substrates do?

Answer 10

Promote cell cycle progression

Question 11

When are CDKs active?

Answer 11

When they are bound by their partners cyclins

Question 12

How do CDK protein levels vary during the cell cycle?

Answer 12

They are mainly stable

Question 13

What happens to cyclin levels during the cell cycle?

Answer 13

They rise and fall

Question 14

What is the result of the rising and falling of cyclin levels during the progression of the cell cycle?

Answer 14

Activation of CDK oscillates

Question 15

Does CDK or cyclin dictate the progression of the cell cycle?

Answer 15

Cyclin, as its levels are rising and falling

Question 16

What CDKs operate during G1?

Answer 16

CDK4-6

Question 17

What cyclins are involved in the G1 phase of the cell cycle?

Answer 17

Cyclin D1, D2, and D3

Question 18

What CDKs are involved in the G1/S phase of the cell cycle?

Answer 18

CDK2

Question 19

What cyclins are involved in the G1/S phases of the cell cycle?

Answer 19

Cyclin E1, E2

Question 20

What CDKs are involved in the S phase of the cell cycle?

Answer 20

CDK2

Question 21

What cyclins are involved in the S phase of the cell cycle?

Answer 21

Cyclin A1, A2

Question 22

What CDKs are involved in the M phase of the cell cycle?

Answer 22

CDK1

Question 23

What cyclins are involved in the M phase of the cell cycle?

Answer 23

Cyclin B1

Question 24

What cyclins and CDKs are essential for entry into G1?

Answer 24

CyclinD/CDK4-6

Question 25

What cyclins and CDKs regulate G1 to S progression?

Answer 25

CyclinE/CDK2

Question 26

What cyclins and CDKs are required during S and G2 phases

Answer 26

CyclinA/CDK2

Question 27

What do cyclinA/CDK2 do during S and G2 phases?

Answer 27

Triggers DNA polymerase activity

Question 28

What cyclins and CDKs promote entry into mitosis?

Answer 28

CyclinB/CDK1

Question 29

What is RB?

Answer 29

A tumour supressor gene

Question 30

How does RB act as a tumour suppressor gene?

Answer 30

Rb binds to E2F, which inhibits it from transcribing its S-phase genes

Question 31

What are the S phase genes produced by E2F responsible for?

Answer 31

* DNA synthesis * DNA replication * DNA repair * Regulation (via Cyclin E and Cyclin A)

Question 32

What cyclin/CDK complex activates RB?

Answer 32

Cyclin D and CDK4/6

Question 33

How is Rb inactivated?

Answer 33

Phosphorylation by cyclinE/CDK2

Question 34

What regulates phosphorylation of Rb by cyclinE/CDK2?

Answer 34

Cyclin E

Question 35

What effect does the HPV virus have on Rb?

Answer 35

It produces the E7 protein, which binds and inactivated Rb

Question 36

What acts as negative regulation of the cyclinD and CDK4/6 complex?

Answer 36

INK4 *(**IN**hibitor of **K**inase **4**)*

Question 37

What produces the INK4 complexes?

Answer 37

* p16 produces INK4a * p15 produces INK4b * p18 produces INK4c * p19 produces INK4d

Question 38

How do the INK complexes act as negative regulators of CDK4?

Answer 38

They bind CDK, and block interaction with cyclin so the complex cannot form and therefore it cannot be activated

Question 39

What factors act as positive regulation CDK4?

Answer 39

* Growth factor * MAPK * Myc oncogene * PI3K/AKT

Question 40

What acts as a negative regulator for cyclinE/CDK2?

Answer 40

CDK-interacting protein (CIP) or kinase inhibitor protein (KIP)

Question 41

What produces the CIP and KIP proteins?

Answer 41

* p21 produces CIP1 * p27 produces KIP1 * p57 produces KIP2

Question 42

What are the stages of mitosis?

Answer 42

1. Prophase 2. Prometaphase 3. Metaphase 4. Anaphase 5. Telophase

Question 43

What is the most important phase of mitosis to be regulated?

Answer 43

Prophase -\> metaphase

Question 44

Why is it important to regulate prophase -\> metaphase?

Answer 44

Because there is no way back after metaphase

Question 45

What promotes entry into M phase?

Answer 45

Cyclin A/CDK1

Question 46

What is essential for M phase progression into metaphase?

Answer 46

CyclinB/CDK1

Question 47

What does CDK1 do?

Answer 47

Phosphorylates substrates involved in; * Nuclear envelope breakdown * Chromosome condensation * Mitotic spindle assembly

Question 48

What are cyclinA/B and CDK1 targets of?

Answer 48

E2F