The Cell Cycle and Cancer

Question 1

What happens in G1 checkpoint?

Answer 1

Makes sure there is enough energy and senses external cues, e.g. needing space

Question 2

What happens in G2 checkpoint?

Answer 2

Mainly detects DNA damage and sees if the cell can repair them

Question 3

What happens in M checkpoint?

Answer 3

Allows chromosomal segregation to occur correctly

Determines if the chromosomes are attached correctly to the microtubule

Question 4

When are CDKs active?

Answer 4

When cyclins are bound

Question 5

What do CDKs do?

Answer 5

Phosphorylate a number of proteins which drive the cell cycle

Question 6

Why are CDKs inactive normally?

Answer 6

Their active sites are blocked so their is no substrate or ATP binding

Question 7

What is the role of cyclins?

Answer 7

To activate CDKs

They provide substrate specificity

Question 8

What do mitogens do?

Answer 8

Activate TFs, e.g. Myc and Fos, to induce cyclin D

Question 9

What does E2F do?

Answer 9

Induce cyclin E and A

Question 10

What does FoxM1 do?

Answer 10

Induces cyclin B

Question 11

What does cyclin D activate?

Answer 11

E2F

Question 12

What does cyclin A activate?

Answer 12

FoxM1

Question 13

What ubiquitin ligases degrade cyclin E?

Answer 13

SCF ligase (Skp, Cullin and F-box)

Question 14

What ubiquitin ligase degrades cyclin A and B?

Answer 14

Anaphase promoting complex/ Cyclosome (APC/C)

Question 15

What is the advantage of sing protein degradation in the cell cycle?

Answer 15

Unidirectional movement

Question 16

Describe the positive feedback mechanism of cyclinB:CDK1

Answer 16

CyclinB:CDK1 is inhibited by Wee1/My1 which causes CDK1 phosphorylation
When cyclinB:CDK1 is in the active conformation, it inhibits Wee1/My1 and activates CDC25 phosphatase to dephosphorylate CyclinB:CDK1 so more is in the active conformation

Question 17

Describe the positive feedback mechanism of cyclinE:CDK2

Answer 17

Mitogens induce the binding of p27 (inhibitor) to cyclinE:CDK2
When cyclinE:CDK2 is in the positive conformation, it phosphorylates and inhibits p27

Question 18

What inhibits the phosphorylation of p27 by CyclinE:CDK2?

Answer 18

SCF ligase

Question 19

When is E2F in an inactive form?

Answer 19

When it is bound to Rb

Question 20

What inhibits the binding of Rb to E2F?

Answer 20

Phosphorylation by CyclinD:CDK4/6

Question 21

What stimulates CyclinD:CDK4/6?

Answer 21

Growth conditions

Question 22

What percentage of tumours are aneuploid?

Answer 22

80-90%

Question 23

What is chromosomal instability caused by?

Answer 23

Frequent errors in mitosis

Question 24

What is chromosomal instability associated with?

Answer 24

Poor patient prognosis
Metastasis
Resistance to chemotherapies

Question 25

What phenotype is worse, having too many or too little chromosomes?

Answer 25

Having too many

Question 26

What happens during the mitotic checkpoint?

Answer 26

Unattached kinetochores produce mitotic checkpoint complex (MCC) -> Inhibits the anaphase promoting complex (APC) -> when all kinetochores are attached then MCC production stops -> APC becomes active and degrades Cyclin B and Securin -> Mitosis

Question 27

How do microtubules bind to kinetochores?

Answer 27

Randomly | Negatively charged microtubules bind to positively charged kinetochores

Question 28

What is securin?

Answer 28

An inhibitor of separase

Question 29

What is separase function?

Answer 29

It cleaves the bond which holds sister chromatids together

Question 30

What is the process of error correction?

Answer 30

Aurora B removes kinetochore-microtubule attachments -> Correct attachments pull away from aurora B -> These are then insensitive to aurora B -> Allows specific correction of attachment errors

Question 31

In terms of the cell cycle, why are tumour suppressors important?

Answer 31

Without tumour suppressors, the cyclins are not degraded and cell cyclin will continue when it is not meant to

Question 32

What CDK binds to cyclin E?

Answer 32

CDK2

Question 33

What CDK binds to Cyclin D?

Answer 33

CDK4/6

Question 34

What CDK does Cyclin B bind to?

Answer 34

CDK1