Checkpoint focus — In the normal eukaryotic cell cycle, which boundary is the principal checkpoint that integrates growth signals and DNA integrity before genome replication?

Introduction / Context:
Cells commit to DNA replication only after assessing growth factors, nutrient status, and DNA damage. The key decision point is the G1–S boundary, often called the restriction point (mammals) or Start (yeast). Correctly identifying this checkpoint underpins understanding of cancer biology and therapeutics.

Given Data / Assumptions:

• Mitogens and nutrients drive cyclin D–CDK4/6 and cyclin E–CDK2 activity.
• DNA damage checkpoints can block S-phase entry by activating p53/p21 pathways.
• Once past the restriction point, the cell is largely committed to complete a cycle.

Concept / Approach:
The G1–S checkpoint integrates external and internal cues. Passing this checkpoint initiates DNA synthesis. Other boundaries exist (S–G2, G2–M, metaphase–anaphase), but the primary commitment control is G1–S.

Step-by-Step Solution:

Verification / Alternative check:
CDK inhibitors that block cyclin D/E complexes specifically prevent S-phase entry, illustrating the centrality of the G1–S checkpoint.

Why Other Options Are Wrong:

• a/b/d/e: Important transitions but not the main growth-factor-integrating checkpoint.

Common Pitfalls:
Assuming metaphase alignment is a growth checkpoint; it monitors spindle attachment, not growth signals.

Final Answer:
G1–S boundary (restriction point/start)