Question 1

What role does S-Cdk play in initiating DNA replication?

Accepted Answer

S-Cdk, a cyclin-dependent kinase, is the primary molecular trigger for DNA replication initiation. It phosphorylates key licensing factors and replication proteins, converting cells from G1 phase into S phase. This activation marks the commitment point where the cell begins duplicating its entire genome, a critical step within the cell cycle.

Question 2

How does S-Cdk differ from other cyclin-dependent kinases?

Accepted Answer

S-Cdk is specifically active during S phase and targets replication machinery proteins, whereas other Cdks regulate different cell cycle transitions. S-Cdk's substrate specificity and timing distinguish it as the primary replication initiator, making it essential for coordinating DNA synthesis with other cell cycle events.

Question 3

What happens to licensing factors when S-Cdk becomes active?

Accepted Answer

S-Cdk phosphorylates licensing factors like Cdt1 and Cdc6, preventing them from rebinding to chromatin. This phosphorylation ensures DNA replicates only once per cell cycle by blocking re-licensing of origins that have already fired, maintaining genomic stability and preventing gene amplification.

Question 4

Why is S-Cdk activity restricted to S phase?

Accepted Answer

S-Cdk activity is tightly regulated by cyclin S levels, which rise only during S phase. This temporal restriction ensures DNA replication initiates at the appropriate time and prevents inappropriate re-replication. Once S phase ends, cyclin S degradation inactivates S-Cdk until the next cell cycle.

Question 5

What proteins does S-Cdk phosphorylate to activate replication origins?

Accepted Answer

S-Cdk phosphorylates origin recognition complex proteins and helicase loader proteins, facilitating the assembly of replication machinery at origins of replication. These phosphorylation events promote the loading of MCM2-7 helicases and other initiation factors required to unwind DNA and begin synthesis.

Question 6

How does S-Cdk prevent re-replication of DNA?

Accepted Answer

S-Cdk phosphorylates and inactivates licensing factors, preventing them from re-loading onto replicated DNA. This mechanism ensures each chromosomal region replicates exactly once per cell cycle. The inhibition persists until licensing factors are dephosphorylated in the next G1 phase, maintaining genomic integrity.

Question 7

What is the relationship between S-Cdk activation and G1/S transition?

Accepted Answer

S-Cdk activation marks the G1/S checkpoint transition, committing cells to DNA replication. Rising S-cyclin levels drive S-Cdk activity, which phosphorylates substrates that both activate replication origins and prevent re-licensing. This dual action ensures orderly progression through the cell cycle and prevents genomic instability.

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