Regulation of Cell Cycle Progression- Lecture 52

Question 1

Describe the Cdk phosphorylation of substrates for the G1 phase.

Answer 1

Kinase: Cdk4 and 6
Cyclin: D
Mechanism of increasing cyclin: Growth factor signaling
Substrate: pRb
Effect: Cyclin E increase

Question 2

Describe the Cdk phosphorylation of substrates for the G1-S phase.

Answer 2

Kinase: Cdk2
Cyclin: E
Mechanism of increasing cyclin: E2F release from Rb
Substrate: pRb
Effect: DNA pol increase etc. and Cyclin A increase

Question 3

Describe the Cdk phosphorylation of substrates of substrates for the S phase.

Answer 3

Kinase: Cdk2
Cyclin: A
Mechanism of increasing cyclin: E2F release from Rb
Substrate: polymerase complex and Cdc6/Orc1/Cdt1
Effect: origin of firing/ block of re-initiation

Question 4

Describe the Cdk phosphorylation of substrates for the M phase.

Answer 4

Kinase: Cdk1
Cyclin: B
Mechanism of increasing cyclin: Loss of repressor
Substrate: lamins and condensin
Effect: nuclear membrane breakdown and chromatin condensation

Question 5

Name the cell cycle checkpoints.

Answer 5

Restriction point (G1)
DNA damage checkpoints (G1-->S and G2-->S)
Unreplicated DNA
Spindle Checkpoint

Question 6

The loss of checkpoint control leads to ______.

Answer 6

uncontrolled proliferation (cancer).

Question 7

What mediates the restriction point?

Answer 7

pRb phosphorylation in response to growth factors (this is lost in cancers)

Question 8

What occurs in the G1 checkpoint?

Answer 8

DNA damage causes up-regulation of p53 (tumor suppressor)
kinase cascade results in phosphorylation of p53 adn Mdm2 (ubiquitin ligase for p53)
phosphorylation disrupts binding and p53 levels rise (transcription factor for p21)
p21 (cyclin-dependent kinase inhibitor) is upregulated, binds to Cdk adn prevents phosphorylation of pRb
cell arrest and apoptosis

Question 9

What occurs in the G2 checkpoint?

Answer 9

DNA damage triggers a kinase cascade
inhibitory phosphorylation of Cdc25
no activation of Cyclin B/Cdk1
Cdc25 in its phosphorylated form is not present until DNA synthesis is complete and a full 4N is achieved

Question 10

How is the spindle checkpoint triggered?

Answer 10

disruption of the spindle and loss of attachment of microtubules to the kinetochore causing delay in activation of APC