Questions: Centrosome Function and Microtubule Organizing Centers

Question 1

What would most likely happen if a cell had a mutation preventing centrosome duplication during S phase?

• A. The cell would fail to replicate its DNA because centrosomes are required for replication
• B. The cell would enter mitosis with one centrosome, forming an asymmetric spindle that risks unequal chromosome distribution
• C. The cell would immediately undergo apoptosis because centrosomes are required for survival signals
• D. Transcription would halt because centrosomes organize gene expression

Answer: (B)

Centrosome duplication in S phase produces two centrosomes that separate to become bipolar spindle poles in mitosis. Without duplication, the cell enters mitosis with one centrosome and cannot form a proper bipolar spindle — leading to a monopolar or asymmetric arrangement that cannot correctly segregate chromosomes to two daughter cells. Centrosomes are not required for DNA replication or transcription; their role is specifically in organizing the mitotic spindle.

Question 2

A cancer cell is found to have four centrosomes instead of two. Which outcome is most directly caused by this amplification?

• A. Faster DNA replication due to additional replication origins at each centrosome
• B. Multipolar mitotic spindles that pull chromosomes in more than two directions, causing missegregation
• C. Permanent cell cycle arrest because the spindle assembly checkpoint detects extra centrosomes
• D. Increased transcription of oncogenes because centrosomes activate gene expression programs

Answer: (B)

Centrosome amplification causes multipolar spindles — three or more poles pulling chromosomes in multiple directions. This leads to chromosomal missegregation. While some cells survive by clustering extra centrosomes into a pseudo-bipolar arrangement, this introduces merotelic attachments producing chromosomal instability (CIN): persistent gains and losses of whole chromosomes. CIN is a hallmark of many aggressive cancers, which is why centrosome amplification correlates with poor prognosis.

Question 3

The γ-TuRC in the centrosome caps the minus end of each microtubule it nucleates, so the growing plus end extends outward into the cytoplasm.

• T. True
• F. False

Answer: True

γ-TuRC (gamma-tubulin ring complex) provides the minus-end template from which alpha/beta-tubulin dimers polymerize. Because it caps the minus end, microtubules grow only from their plus ends — extending outward from the centrosome toward the cell periphery. This directionality creates the radial array of microtubules emanating from the centrosome and, during mitosis, the spindle fibers that attach to chromosomes at their kinetochores.

Question 4

Centrosome duplication is a conservative process: the two original centrioles are degraded, and two mostly new centrosomes are assembled during S phase.

• T. True
• F. False

Answer: False

Centrosome duplication is semi-conservative, analogous to DNA replication. Each existing centriole serves as a template for assembling one new centriole. By G2, each centrosome contains one old (mother) centriole and one new (daughter) centriole. The original centrioles are not degraded — they persist and are distributed to daughter cells. This semi-conservative mechanism ensures each daughter cell inherits a fully functional centrosome.

Question 5

Why does centrosome amplification cause chromosomal instability rather than simply killing the cell in the division where it first occurs?

Model answer: Extra centrosomes can cluster together to form pseudo-bipolar spindles, allowing the cell to divide and survive. However, clustering introduces errors in chromosome-spindle attachments (merotelic attachments), causing some chromosomes to be pulled toward the wrong pole at a low but persistent rate. Each division produces daughters with slightly abnormal chromosome numbers, which continue dividing and accumulating further errors — ratcheting up instability over generations rather than causing immediate cell death.

Chromosomal instability is a rate, not a single catastrophic event. Clustering allows survival at the cost of ongoing missegregation. Each affected division has an elevated chance of producing aneuploid daughters, and those daughters can accumulate additional chromosome imbalances over time. This compounding instability drives cancer progression — it is the mechanism by which centrosome amplification contributes to aggressive tumor behavior rather than simply eliminating aberrant cells.