Cell-cycle checkpoints: The commitment to begin DNA replication is primarily controlled at which checkpoint stage?

Introduction / Context:
Cell-cycle checkpoints ensure that each stage proceeds only when prerequisites are met. The decision to enter S phase and replicate DNA is tightly regulated to prevent genome instability. Identifying the checkpoint controlling this commitment is central to understanding how cells maintain integrity and how cancer can arise.

Given Data / Assumptions:

• S-phase entry is a controlled transition.
• Checkpoints exist in G1, G2, and M; intra-S surveillance also occurs.
• Question asks which checkpoint primarily governs initiation of DNA replication.

Concept / Approach:
The G1 checkpoint (restriction point in mammals; Start in yeast) integrates growth signals, nutrients, DNA damage status, and cell size. Passage through this point commits the cell to S phase. If conditions are unfavorable, cells delay S-phase entry or enter G0. While an intra-S checkpoint monitors ongoing replication and responds to damage or stalled forks, the initial go/no-go decision is made at G1.

Step-by-Step Solution:

Verification / Alternative check:
Pathways involving cyclin D/Cdk4-6 and RB phosphorylation regulate E2F activity at G1; RB inactivation permits transcription of S-phase genes and origin firing.

Why Other Options Are Wrong:

Common Pitfalls:
Confusing the monitoring of replication quality (S checkpoint) with the gatekeeper decision to begin replication (G1 restriction point).

Final Answer:
G1 checkpoint (restriction point/start).