Millonig - Cell Division Regulation

Question 1

4 Classes Cdks

Answer 1

G-Cdk (Pass through restriction point)
G/S (commit to replication)
S (initiate replication)
M (promote mitosis)

Question 2

Orc Complex

Answer 2

Initiates DNA replication in S phase. Inactive state binds to Cdc6 and Mcm- ready for replication but inactive. S-Cdk phosphorylizes complex, Cdc6 is degraded, Mcm (helicase) activates, and DNA synthesis takes place

Question 3

M-Cdk Regulation

Answer 3

M-Cdk1 binds M-cyclin. Phosphorylated by CAK1 (Cdk-activating kinase 1) and Wee1, the Wee phosphate inactivates complex. Then, Cdc25 (phosphatase) removes the phosphate to activate the complex.
Positive Feedback: M-Cdk inhibits Wee1, and activates Cdc25.
Inactivation: M-cdk degraded by proteosome, so irreversible

Question 4

How prevent Cdk activity during G1?

Answer 4

1) Ubiquitin degradation of Cdks
2) Cyclin Kinase Inhibitor (CKI) accumulation
3) Less cyclin transcription

Question 5

Retinoblastoma Protein (Rb) and E2F

Answer 5

Binds and inhibits E2F, a transcription factor for entering S-phase. When cell is ready for S-phase, G1-Cdk accumulates, phosphorylates Rb, releasing E2F to cause S-cyclins to be produced.
-Positive Feedback: E2F causes more G1-Cdk, phosphorylating more Rb, producing more E2F..

Question 6

Retinoblastoma

Answer 6

Caused by lack of Rb production, since constant DNA synthesis without Rb inhibition of E2F

Question 7

G2 Checkpoint

Answer 7

DNA damage inhibits Cdc25 (preventing Wee1 inactivation and M-Cdk dephosphorylation), so cell wont enter mitotic cycle yet

Question 8

G1 Checkpoint

Answer 8

Inhibits G1-Cdk and S-Cdk, preventing entry to S-phase. Uses P53- P53 creates CKI which inhibits the Cdks. Loss of P53 causes uncontrolled proliferation

Question 9

Cdk’s (Cyclin Dependent Kinases)

Answer 9

Phosphorylize proteins downstream to initiate/regulate mitotic events
-dependent on Cyclins to activate (M-cyclin binds to enter M-phase, S for S-phase..)