Cell cycle control — At which checkpoint is progression through mitosis specifically monitored by the spindle assembly (anaphase-promoting) checkpoint?

Difficulty: Medium

Correct Answer: M checkpoint (spindle assembly checkpoint during metaphase–anaphase transition)

Explanation:


Introduction / Context:
Cell-cycle fidelity relies on multiple checkpoints that sense DNA integrity and chromosome attachment. The checkpoint that governs entry into anaphase is crucial to prevent aneuploidy by ensuring every chromosome is bi-oriented and under tension.


Given Data / Assumptions:

  • Key checkpoints: G1 (restriction point), G2/M (DNA damage completion), M (spindle assembly), and intra-S (replication stress).
  • The anaphase-promoting complex/cyclosome (APC/C) triggers separase activation only after checkpoint satisfaction.


Concept / Approach:
The spindle assembly checkpoint (M checkpoint) monitors kinetochore attachment and tension. Unattached kinetochores generate a ‘‘wait’’ signal (MAD2/BUBR1 pathway) that inhibits APC/C. Once satisfied, APC/C degrades securin and cyclin B, allowing anaphase onset and mitotic exit.


Step-by-Step Solution:

Identify which checkpoint directly regulates the mitotic metaphase–anaphase transition.Match that to the M checkpoint/spindle assembly checkpoint.Confirm other checkpoints operate at different stages (G1 restriction, G2/M DNA damage, intra-S replication).


Verification / Alternative check:
Pharmacologic spindle poisons (e.g., nocodazole) activate the spindle checkpoint, arresting cells in metaphase by preventing APC/C activation.


Why Other Options Are Wrong:

  • a/b/d: Important but not the mitosis-specific spindle checkpoint.
  • e: Cytokinesis is downstream of chromosome segregation and not the primary control point for starting anaphase.


Common Pitfalls:
Confusing the G2/M DNA damage checkpoint with the spindle assembly checkpoint; they operate via distinct sensors and effectors.


Final Answer:
M checkpoint (spindle assembly checkpoint during metaphase–anaphase transition)

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