cell replication

Question 1

• What are the stages of the cell cycle?

Answer 1

Duplication

Division

Co-ordination

Question 2

what factors affect the time take for cells to divide

Answer 2

Embryonic VS adult cells

complexity of system eg for yeast cells, only 1.5- 3 hours

Necessity for renewal eg intestinal epithelial 20hrs, hepatocytes is once per yr

Question 3

• Which phases make up Interphase?
• What is the M phase?
• What is the quiescent phase?

Answer 3

G1
S (DNA replication)
G2

Mitosis (nuclear division) and cytokinesis

Inactive stage that occurs when the cell leaves the cell cycle- G0
It may stay in this phase until it is triggered externally to initiate G1 phase

Question 4

What are the checkpoints in cell cycle?

• G1-S checkpoint
• G2-M checkpoint
• during M phase
• during G1 phase

Answer 4

check if enough nutrients/ growth factors

check if DNA is abnormal/ replicated incorrectly
if it is, DNA repair
if not, undergo apoptosis

if chromosomes are properly attached to spindle

if DNA is damaged

Question 5

• How might cells leave G0?

Answer 5

Response to extracellular factors eg tyrosine kinase

growth factors signal cell to go from G0 to G1 phase

Signal amplification

Signal integration by other pathways

Ras/Raf/MEK/ERK (increase protein synthesis and decrease protein degradation)

leading to increased cell growth

Question 6

• What is c-Myc?

- What oncogene causes progression of cell from G0 to S phase and how does it do this?

Answer 6

transcription factor - stimulates the expression of cell cycle genes
oncogene - over-expressed in many tumours

c-Myc
Increases concentration of Cyclin D

Question 7

• What is the purpose of Cyclin dependent kinase (Cdk)?
• Where are Cdks found?
• When are Cdks active?

Answer 7

Phosphorylation and dephosphorylation at serine/threonine/tyrosine
part of signalling events

All proliferating cells

Only when bound to cyclin

Question 8

why are CDKs only sequentially active?

what do CDK- cyclin complexes do?

Answer 8

as they are only active when bound to cyclin, and cyclin concentrations fluctuate within cycle

stimulate synthesis of genes required for next phase
gives direction and timing to cycle

Question 9

which cyclin- Cdk complex drives cell into

• G0 to G1
• G1 to S
• S to G2
• G2 to M
• M to end of cell division

Answer 9

Growth factor induces expression of C-myc, driving cell into G1

C myc stimulates expression of Cyclin D, which binds to CDK 4/6

CyclinD-CDK4/6 complex stimulates expression of cyclin E, which binds to CDK2

Cyclin A and CDK2

Cyclin B and CDK 1

Question 10

• What effect does phosphorylation have on kinases?

- What effects does phosphatases have on kinases?

Answer 10

Activates them

Turns them off (if removing an activating phosphatase)

Question 11

• How are Cdks activated?

Answer 11

Cyclin produced and binds to Cdk

Phosphorylation of Cdk-cyclin complex at inhibitory and activating sites of Cdk

Phosphatase removes inhibitory phosphate from Cdk, activating it

Question 12

• How does positive feedback work to increase the amount of active Cdk?
• Explain the process by which cyclins are turned off?

Answer 12

The activated Cdk activates more of the phosphatase to remove further inhibitory phosphates from Cdk-cyclin complexes

Cyclin is ubiquitylated (tagged)
Leading to destruction of cyclin
And so Cdk is inactive

Question 13

• Which Cyclin-Cdk complex leads to the progression into S phase?
• Which Cyclin-Cdk complex leads to the progression into M phase?

Answer 13

Cyclin S - Cdk Complex

Cyclin M - Cdk Complex

Question 14

• How does the activity of the cyclins allow the cell cycle to be cyclical?
• What is Retinoblastoma?

Answer 14

The cyclins are susceptible to degradation, so they can be formed again

Tumour suppressor

Question 15

• How is Retinoblastoma involved in cell proliferation?

Answer 15

Activation of intracellular signalling leads to production of activated Cdk

They phosphorylate the active Retinoblastoma that is bound to the TF, inactivating it

This causes the Retinoblastoma to release the TF which then targets activation of genes such as DNA polymerase and thymidine kinase

Question 16

• What is the function of p53?

– How does p53 act as a tumour suppressor?

Answer 16

They stop cells with damaged DNA in G1 to move onto next phase

When double stranded DNA damage occurs, p53 is not degraded
p53 is activated via phosphorylation
It binds to and activates the transcription and translation of p21
The enzyme (CDK inhibitor protein) formed by expression of p21 inhibits the action of the Cyclin-Cdk complex
So the cell cycle can no longer continue