Chromosome Segregation

Chromosome Segregation

During cell division, duplicated chromosomes must be evenly distributed to daughter cells. This requires sister chromatids to attach to microtubules from opposite spindle poles (bi-orientation) before they can be separated at anaphase.

Spindle Assembly Checkpoint (SAC)

The SAC monitors kinetochore-microtubule attachments and prevents anaphase until all chromosomes are properly bi-oriented. Unattached or incorrectly attached kinetochores generate a "wait" signal that inhibits the anaphase-promoting complex (APC/C).

Attachment Types

• Amphitelic (correct): Sister kinetochores attached to opposite poles
• Syntelic: Both sisters attached to the same pole
• Merotelic: One kinetochore attached to both poles
• Monotelic: Only one kinetochore attached

Aurora B Error Correction

Aurora B kinase phosphorylates kinetochore substrates to destabilize incorrect attachments. The key is tension: correct bi-oriented attachments are under tension (sister chromatids pulled in opposite directions), which spatially separates substrates from Aurora B. Incorrect attachments lack tension, keeping substrates in the Aurora B activity zone.

Consequences of Errors

Uncorrected attachment errors lead to chromosome missegregation and aneuploidy (abnormal chromosome number). Aneuploidy is a hallmark of cancer and causes developmental disorders like Down syndrome (trisomy 21).