Cells with extra centrosomes undergo bipolar cell divisions but display a significantly elevated frequency of lagging chromosomes during anaphase, resulting in chromosome missegregation errors. Extra centrosomes alone are sufficient to promote these segregation errors without requiring multipolar division. [@ganem_mechanism_2009]
Definitions
- centrosomes
- chromosome missegregation
- bipolar cell division
- lagging chromosomes
- anaphase
- multipolar division
Synthesis
Extra centrosomes promote chromosome missegregation during bipolar division through a mechanism that is now well-established across multiple lines of evidence, despite the historical assumption that extra centrosomes would primarily cause problems through multipolar divisions. The key mechanistic insight is that cells with extra centrosomes typically undergo bipolar rather than multipolar division, but they pass through a transient multipolar spindle intermediate state during which merotelic kinetochore-microtubule attachments accumulate before centrosome clustering occurs. These accumulated merotelic errors persist into the bipolar anaphase that follows, manifesting as lagging chromosomes and ultimately driving chromosome missegregation and chromosomal instability. This mechanism explains how centrosome amplification causes chromosomal instability independently of the classic mitotic defects such as spindle assembly checkpoint dysfunction that account for instability in only a small subset of aneuploid tumor cells, though the relative contributions of different attachment error types and the precise dynamics of error accumulation during the multipolar intermediate remain areas of active investigation.
Related
- Multipolar spindle intermediate allows merotelic attachment accumulation
- Multipolar divisions are rare and typically produce inviable progeny
- CIN exists independently of classic mitotic defects in most cells