Cells with extra centrosomes pass through a transient multipolar spindle intermediate state in which merotelymerotelic kinetochore-microtubule attachment errors accumulate before centrosome clustering occurs. This accumulation of merotelic errors precedes the transition to bipolar anaphase and explains the elevated frequency of chromosome missegregation. [@ganem_mechanism_2009]
Definitions
- multipolar spindle intermediate
- merotelymerotelic attachment
- kinetochore
- microtubule
- centrosome clustering
- anaphase
- centrosomes
- chromosome missegregation
Synthesis
Cells with extra centrosomes transiently form a multipolar spindle configuration that must be resolved into a bipolar arrangement through centrosome clustering before division can proceed. During this multipolar spindle intermediate stage, chromosomes experience attachment to microtubules emanating from multiple poles, which creates favorable conditions for the accumulation of merotelic attachments—aberrant connections where a single kinetochore binds microtubules from more than one spindle pole. This mechanistic link establishes how centrosome amplification drives chromosomal instability even when cells ultimately divide in a bipolar fashion, explaining observations that extra centrosomes promote chromosome missegregation during anaphase without requiring completion of multipolar division. The precise dynamics of how merotelic attachments accumulate during the multipolar intermediate and whether all cells with extra centrosomes necessarily transit through such an intermediate remain areas requiring further investigation.
Related
- Merotely causes chromosome missegregation in unstable cells
- Extra centrosomes promote chromosome missegregation during bipolar division
- CIN exists independently of classic mitotic defects in most cells
- Elevated merotely generates CIN in stable near-diploid cells