In eukaryotes, DNA replication must occur with extreme accuracy and only once to prevent the damaging effects of gene amplification. The following statements were made regarding possible mechanisms involved in achieving tight regulation of DNA replication:

A. High APC/C activity in mitosis and early G₁ phase of the cell cycle that triggers the destruction of Cdt1 inhibitor geminin, thus allowing Cdt1 to be active in early G₁ to load helicases.
B. Activation of S-Cdks that regulate the phosphorylation of specific initiator proteins in the S-phase.
C. MCM helicase loads at the S-phase of the cell cycle, so that replication begins only at S-phase.
D. Cdc6 and Cdt1 bind to the origin recognition complex (ORC) and help in pre-replicative complex assembly only after mitosis.

Which one of the options has all correct statements?

Correct option is C

Explanation-

Statement A: High APC/C activity in mitosis and early G1 phase of the cell cycle that triggers the destruction of Cdt1 inhibitor geminin, thus allowing Cdt1 to be active in early G1 to load helicases.
Correct.
APC/C (Anaphase Promoting Complex/Cyclosome) is active during mitosis and early G1. It leads to the degradation of geminin, an inhibitor of Cdt1. Without geminin, Cdt1 is free to help load the MCM helicase onto DNA in early G1.

Statement B: Activation of S-Cdks that regulate the phosphorylation of specific initiator proteins in the S-phase.
Correct.
S-Cdks (S-phase Cyclin-dependent kinases) are essential for initiating DNA replication. They phosphorylate initiator proteins (like Cdc6, Cdt1, ORC complex components), promoting the assembly of the pre-initiation complex.
They also help prevent re-replication.

Statement C: MCM helicase loads at the S-phase of the cell cycle, so that replication begins only at S-phase.
Incorrect.
MCM helicase actually loads during late M phase and early G1, not S-phase. The pre-replication complex (pre-RC) is formed in G1. Activation of the helicase occurs at S-phase, but loading happens before.

Statement D: Cdc6 and Cdt1 bind to the origin recognition complex (ORC) and help in pre-replicative complex assembly only after mitosis.
Correct.
Cdc6 and Cdt1 are key loading factors. They interact with ORC to recruit the MCM complex to replication origins. This occurs in early G1, i.e., after mitosis and before S-phase.

Since the correct Statements is  A, B, D
Thus, the correct option is c -  A, B, and D only