Which of the following statements about initiation of DNA replication in eukaryotes is/are true?
DNA replication is initiated at the origin of replication licensed by loading of Mcm helicase complex
Loading of Mcm helicase complex takes place in S phase
Mcm helicase complex are activated by S-Cdks
Mcm helicase complex is responsible for loading of origin recognition complex
ANSWER
The true statements are (A) and (C): replication origins are licensed by Mcm helicase loading, and the loaded Mcm complex is activated by S-Cdks (together with DDK) to fire origins.
Official answer: A, CSource: Official answer key, GATE 2025 BT (IIT Roorkee)
Origin licensing: in late M/G1 phase, the Origin Recognition Complex (ORC), bound at the origin, recruits Cdc6 and Cdt1, which together load the Mcm2-7 helicase complex onto DNA as an inactive double hexamer. This loading event constitutes licensing of the origin for replication.
Evaluate (A): 'Replication is initiated at the origin licensed by loading of Mcm helicase complex' — TRUE. Licensing is a precondition for firing; only licensed origins can initiate replication.
Evaluate (B): 'Loading of Mcm helicase complex takes place in S phase' — FALSE. Mcm loading (licensing) occurs in G1 phase, before S phase begins, which keeps licensing and firing temporally separated so each origin fires only once per cell cycle.
Evaluate (C): 'Mcm helicase complex are activated by S-Cdks' — TRUE. At the G1/S transition, DDK (Dbf4-dependent kinase) together with S-phase CDKs phosphorylates Mcm-associated firing factors (e.g., Sld2, Sld3/Treslin) and Mcm subunits, converting the loaded pre-RC into the active CMG helicase and triggering origin firing.
Evaluate (D): 'Mcm helicase complex is responsible for loading of origin recognition complex' — FALSE. The order is reversed: ORC binds the origin first and recruits Cdc6/Cdt1 to load Mcm, not the other way around.
Therefore the true statements are (A) and (C).
KEY IDEA
Eukaryotic origin licensing (ORC → Cdc6/Cdt1 → Mcm2-7 double hexamer loading) occurs in late M/G1 phase; origin firing (activation of the loaded Mcm helicase into the active CMG complex) is triggered at the G1/S transition by DDK and S-phase Cdks. Licensing and firing are temporally separated so each origin fires only once per cycle.
WATCH OUT FOR
Confusing the order of events — thinking Mcm loading happens in S phase (it happens in G1, forming the pre-replication complex) or thinking Mcm loads/recruits ORC (it is the reverse: ORC binds first and recruits Cdc6/Cdt1 to load Mcm).
From the GATE 2025 BT paper. Every question of this paper · Download the full paper · All 21 Gene expression questions, with notes
