Section 3: Genetics, Cellular and Molecular Biology
Recombinant DNA technology
Subtopic: Fundamentals of Recombinant DNA technology
Question Statement:
Which of the following statements about initiation of DNA replication in
eukaryotes is/are true?
Options:
(A) DNA replication is initiated at the origin of replication licensed by loading
of Mcm helicase complex
(B) Loading of Mcm helicase complex takes place in S phase
(C) Mcm helicase complex are activated by S-Cdks
(D) Mcm helicase complex is responsible for loading of origin recognition complex
Official Answer Key:
A;C
Step-by-Step Solution & Explanation
### **Official Solution & Concept Analysis (GATE BT 2025 Q.50)**
**1. Governing Concept**:
- **Topic**: Molecular Biology & Eukaryotic DNA Replication Initiation
- Eukaryotic replication initiation occurs in two spatially and temporally distinct phases:
1. **Licensing ($G_1$ phase, low CDK activity)**: The Origin Recognition Complex (ORC1–6) binds origins and recruits Cdc6 and Cdt1 to load the inactive ring-shaped **MCM2–7** replicative helicase hexamer onto double-stranded DNA as an inactive double hexamer.
2. **Activation ($S$ phase, high CDK and DDK activity)**: Dbf4-dependent kinase (DDK) and S-CDK phosphorylate MCM subunits and recruitment factors (Sld3/Treslin, Sld2), recruiting **Cdc45** and the **GINS complex** to convert MCM2–7 into the active **CMG (Cdc45-MCM-GINS)** holo-helicase that unwinds DNA.
**2. Option Analysis**:
- **Option (A) is CORRECT**: MCM2-7 double hexamer is loaded onto replication origins during the G1 phase of the cell cycle (origin licensing).
- **Option (B) is INCORRECT**: CMG complex formation and helicase activation are driven by high CDK and DDK activity during S phase, not G1 phase.
- **Option (C) is CORRECT**: Origin Recognition Complex (ORC) acts as the foundation platform for assembly of the pre-replicative complex (pre-RC).
- **Option (D) is INCORRECT**: Primase synthesizes RNA primers, not origin recognition proteins.
**3. Final Answer**:
- **Correct Options**: **A, C**
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