The following statements were made about cell cycle regulation in fission yeast:

A. A cdc25 mutant cannot enter mitosis due to its inability to remove the inhibitory phosphate.
B. Wee1 consistently maintains the Cdk in an active state, to maintain cell size during the cell cycle.
C. CAK (Cdk-activating kinase)-mediated phosphorylation of Threonine 161 residue of Cdc2 is necessary, but not sufficient, for the Cdk to be active.
D. Activation of Sic1 in G1 allows the cyclin–Cdk that is present in the cell to initiate DNA replication.
E.sic1 mutant exhibits activation of premature DNA replication from fewer origins and extension of the duration of S phase.

Which one of the following options represents the combination of all correct statements?

• Cdc25: A phosphatase that removes inhibitory phosphorylation from Cdc2 (CDK1), allowing mitotic entry.
• Wee1: A kinase that inhibits Cdc2 by phosphorylation, regulating cell size and delaying mitosis.
• CAK (Cdk-Activating Kinase): Phosphorylates Thr161 of Cdc2, which is necessary but not sufficient for full activation.
• Sic1: An inhibitor of S-phase cyclin-CDK, preventing premature DNA replication.
• Sic1 mutant: Causes premature replication and extended S-phase duration.

1. Statement A: "A cdc25 mutant cannot enter mitosis due to its inability to remove the inhibitory phosphate."

   • Correct.
   • Cdc25 is essential for mitosis, as it removes the inhibitory phosphate on Cdc2/CDK1. A cdc25 mutant arrests in G2.

2. Statement B: "Wee1 consistently maintains the Cdk in an active state, to maintain cell size during the cell cycle."

   • Incorrect.
   • Wee1 is an inhibitor, not an activator. It phosphorylates and inactivates Cdc2/CDK1, preventing premature mitosis.

3. Statement C: "CAK (Cdk-activating kinase)-mediated phosphorylation of Threonine 161 residue of Cdc2 is necessary, but not sufficient, for the Cdk to be active."

   • Correct.
   • CAK phosphorylation is needed for activation, but Cdc25 must also remove the inhibitory phosphate for full activation.

4. Statement D: "Activation of Sic1 in G1 allows the cyclin-Cdk that is present in the cell to initiate DNA replication."

   • Incorrect.
   • Sic1 is a CDK inhibitor (CKI) that prevents premature S-phase entry. Its inactivation, not activation, allows DNA replication.

5. Statement E: "sic1 mutant exhibits activation of premature DNA replication from fewer origins and extension of the duration of S phase."

   • Correct.
   • Sic1 normally inhibits S-phase cyclins. If it is mutated, DNA replication initiates prematurely, leading to inefficient origin activation and an extended S phase.

Correct Answer:

• Statements A, C, and E are correct.
• Answer: Option 2 (A, C, and E).