Cell Replication

Question 1

4 main phases of the cell cycle?

Answer 1

G1, `s, G2 (all interphase) and M phase

Question 2

G0 phase?

Answer 2

Cell not dormant but non-dividing

Question 3

4 reasons why cells leave G0?

Answer 3

• Response to extracellular factors
• Signal amplification
• Signal integration/modulation by other pathways
• Ras/Raf/MEK/ERK

Question 4

3 checkpoints?

Answer 4

• G1 checkpoint- is environment favourable?
• G2 checkpoint- Is all DNA replicated and DNA damage repaired?
• Mitosis checkpoint- are all chromosomes properly attached to the mitotic spindle?

Question 5

3 facts about c-Myc?

Answer 5

• Codes for transcription growth factors
• Promotes G0 to G1 transition
• c-Myc is an oncogene- overexpressed in many tumours

Question 6

5 facts about Cdks?

Answer 6

• Phosphorylation and dephosphorylation
• Key signaling events
• Allows control of events
• Present in proliferating cells but only active when cyclin is bound (levels peak in mitosis)
• Cyclins are synthesised and then degraded by ubiquitylation. Ubiquitin molecules are stuck on cyclins and they are degraded into amino acids .

Question 7

3 steps to Cdk activation?

Answer 7

1. Cyclin produced and forms an inactive cyclin-Cdk complex
2. Protein kinases phosphorylates complex
3. Activating protein phosphatase removes inhibiting phosphate group to activate complex

Question 8

3 things protein kinase cascades lead to?

Answer 8

• signal amplification
• diversification
• opportunity for regulation

Question 9

How are cdks regulated?

Answer 9

Interaction with cyclin

Phosphorylation

Question 10

How are cyclins regulated?

Answer 10

Transiently expressed at specific points of the cycle
Regulated at level of expression
Synthesised and then degraded

Question 11

Two things that drive progression of cell cycle?

Answer 11

Induction of cyclins plus phosphorylation

Question 12

How do cyclins give direction and timing to the cell cycle?

Answer 12

They become sequentially active and stimulate synthesis of genes required for next phase

Question 13

Rb?

Answer 13

Mitogen, growth factor, increases protein synthesis and inhibits degradation

Question 14

How does Rb act as a molecular brake?

Answer 14

Active Rb sequesters a TF in an inactive form so the TF’s cannot turn on genes needed for cell cycle progression

Question 15

How is Rb inactivated?

Answer 15

Cdks phosphorylate Rb so the TF can be released

Question 16

p53 mechanism?

Answer 16

• X-rays cause double stranded breaks in DNA
• p53 recognises changes and activates protein kinases that phosphorylate p53 to stabilize and activate it
• Active p53 binds to regulatory region of p21 gene
• p21 proteins produced to inhibit Cdk proteins

Question 17

How does p53 inhibit cdks?

Answer 17

p53 binds to p21 gene and p21 protein inhibits the cdks