Questions: Mitosis: Regulated Chromosome Distribution

Question 1

During mitosis, one kinetochore on a chromosome fails to attach to microtubules from either pole. What happens next?

• A. The cell proceeds to anaphase immediately, since one unattached kinetochore does not significantly delay division
• B. The cell arrests in metaphase — the spindle assembly checkpoint detects the unattached kinetochore and inhibits the APC/C, preventing cohesin cleavage and chromatid separation
• C. The cell skips anaphase and proceeds directly to telophase, distributing chromosomes unequally
• D. The unattached chromosome is degraded, and mitosis continues with the remaining chromosomes

Answer: (B)

The spindle assembly checkpoint (SAC) is exquisitely sensitive: a single unattached or improperly attached kinetochore is sufficient to halt the entire process. The unattached kinetochore generates a 'wait' signal that inhibits the anaphase-promoting complex (APC/C). The APC/C is the ubiquitin ligase that would normally trigger cleavage of the cohesin proteins holding sister chromatids together. As long as the inhibitory signal persists, anaphase cannot begin. Only when all kinetochores are properly attached to microtubules from opposite poles is the checkpoint satisfied and division allowed to proceed.

Question 2

What is the functional significance of chromosomes aligning at the metaphase plate before anaphase begins?

• A. Alignment at the equator allows chromosomes to condense fully before being separated
• B. Alignment ensures that each kinetochore is under tension from microtubules attached from opposite poles, which the spindle assembly checkpoint uses to confirm correct bi-orientation before allowing chromatid separation
• C. Alignment reduces the distance chromosomes must travel to reach each pole, speeding up anaphase
• D. Alignment at the metaphase plate is merely an artifact of balanced pulling forces with no regulatory significance

Answer: (B)

Metaphase plate alignment is not incidental — it reflects a mechanically verified state. A chromosome is bi-oriented when microtubules from both poles attach to its two sister kinetochores and place the chromosome under tension at the equator. This tension is sensed by the kinetochore and signals correct attachment. Chromosomes pulled toward only one pole (mono-oriented) are not under this tension and continue to generate the 'wait' signal. The metaphase plate is therefore a visual indicator that bi-orientation — and hence checkpoint satisfaction — is being achieved across all chromosomes.

Question 3

In anaphase of mitosis, homologous chromosomes separate to opposite poles.

• T. True
• F. False

Answer: False

This is the most common confusion between mitosis and meiosis. In anaphase of mitosis, sister chromatids separate to opposite poles — the cohesin holding the two copies of each replicated chromosome is cleaved, and each copy moves to a different pole. Homologous chromosome separation occurs in anaphase I of meiosis (the reductive division). Mitosis produces two genetically identical daughter cells, each with the same chromosome number as the parent; meiosis I produces cells with half the chromosome number by separating homologs.

Question 4

The spindle assembly checkpoint can delay anaphase onset indefinitely, regardless of how many kinetochores are unattached, until all kinetochores achieve proper bi-oriented attachment.

• T. True
• F. False

Answer: True

The checkpoint operates as a zero-tolerance system: as long as even one kinetochore remains unattached or incorrectly attached, it continues to produce inhibitory signals that block APC/C activation. This is not a counting mechanism that tolerates a few errors — it is an all-or-nothing gate. The biological logic is clear: if even one chromosome is misattached and distributed incorrectly, the daughter cells receive the wrong chromosome number (aneuploidy), which can cause developmental defects or cancer. The checkpoint's stringency ensures near-perfect fidelity.

Question 5

Explain how the spindle assembly checkpoint prevents aneuploidy, and describe what happens in cells where this checkpoint fails.

Model answer: The spindle assembly checkpoint monitors kinetochore attachment during metaphase. Any unattached or mono-oriented kinetochore produces an inhibitory signal that prevents the anaphase-promoting complex (APC/C) from triggering cohesin cleavage. This delays anaphase until all chromosome pairs achieve bi-orientation — attachment by microtubules from opposite poles under tension. When the checkpoint is satisfied, the inhibitory signal ceases, APC/C is activated, cohesin is cleaved, and sister chromatids separate to opposite poles with high fidelity. When the checkpoint fails (as it commonly does in cancer cells due to mutations in checkpoint components), cells proceed to anaphase with improperly attached chromosomes, resulting in daughter cells with extra or missing chromosomes (aneuploidy). Aneuploidy drives genomic instability and contributes to tumor progression.

The key insight is that the checkpoint is a surveillance system, not a timer. It does not wait a fixed amount of time — it actively monitors attachment state and releases the brake only when mechanical bi-orientation is confirmed. Failure is catastrophic at the cellular level because each misattached chromosome produces one aneuploid daughter, and aneuploidy is associated with nearly all solid tumor cancers.