4) Cell Cycle

Question 1

What are the stages of the cell cycle?

Answer 1

Mitosis

Interphase: G1, S, G2

Question 2

Describe the changes to DNA content in the cell during the stages of the cell cycle:

Answer 2

G1 - 2N diploid
S - 2N-4N
G2 - 4N tetraploid
M - 4N-2N

Question 3

Describe the function of CDKs:

Answer 3

Serine/threonine kinases which promote cell cycle progression when bound to cyclins

Question 4

How do CDK and cyclin levels change during the cell cycle?

Answer 4

CDK protein levels mainly stable, cyclin levels rise and fall so activation of CDK oscillates

Question 5

What CDK/cyclin complexes are needed in G1?

Answer 5

CyclinD/CDK4-6

Question 6

What CDK/cyclin complex are needed in G1 to S progression

Answer 6

CyclinE/CDK2

Question 7

What CDK/cyclin complex are needed in S and G2 phases and why?

Answer 7

CyclinA/CDK2

Triggers polymerase activity

Question 8

What CDK/cyclin complex promotes entry into mitosis?

Answer 8

CyclinB/CDK1

Question 9

How do CDK/cyclin complexes interact with pRB and E2F in G1?

Answer 9

CDK complex phosphorylates RB to allow E2F to carry out transcription of S phase genes

Question 10

What factors positively regulate the cyclinD/CDK4-6 complex?

Answer 10

Growth factor, MAPK, myc oncogene, PI3K

Question 11

What factors negatively regulate the cyclinD/CDK4-6 complex and how?

Answer 11

Inhibitor of kinase 4 (INK4)
p16, p15, p18, p19
Bind CDK4 to prevent complex forming

Question 12

What factors negatively regulate the cyclinE/CDK2 complex and how?

Answer 12

CDK-interacting protein/kinase inhibitor protein
p21-CIP1, p27-KIP1
Bind to complex and inhibit the kinase activity

Question 13

How does p16 (INK4A) protect from cancer?

Answer 13

Protects against lots of oncogenic activity due to mutations e.g. in moles

Question 14

Give examples of cancers in which p16 is lost:

Answer 14

Pancreatic cancer, T cell ALL, glioblastoma

Question 15

Give examples of cancer in which cyclin D1/CDK4 is overexpressed:

Answer 15

Mantle cell lymphoma, breast cancer

Question 16

How does CDK1 promote progression through mitosis?

Answer 16

CDK1 phosphorylates substrates involved in nuclear envelop breakdown, chromosome condensation and mitotic spindle assembly

Question 17

How is the cyclinB/CDK1 activated?

Answer 17

Activated by CDC25 phosphatase removing the phosphates that inactive the complex

Question 18

How is the cyclinB/CDK1 inactivated in the case of DNA damage?

Answer 18

If there is damage kinase check 1 is activated and causes wee1 to phosphorylate the complex

Question 19

Explain the spindle assembly checkpoint:

Answer 19

Allows mitosis to continue if the chromosomes are properly attached to the spindle apparatus. If there is go signal, SAC promotes degradation of cyclin B for mitosis progression

Question 20

What is the result of a defective spindle assembly checkpoint?

Answer 20

Aneuploidy - gain or loss of entire chromosomes

Question 21

Why are broad spectrum CDK inhibitors ineffective?

Answer 21

Need to be used at higher dose (toxic)

CDKs exist that have functions outside of the cell cycle

Question 22

Give examples of CDK4/6 selective inhibitors:

Answer 22

Palbociclib, ribociclib

Question 23

How does HPV interact with Rb?

Answer 23

HPV produces E7 proteins that binds and inactivates Rb