By using long-term live-cell imaging to visualize thousands of cell divisions in cancer cell lines, the authors found that cells with multiple centrosomes rarely undergo multipolar cell divisions and, even when they do, they produce progeny that usually die or arrest, challenging the commonly held belief that multipolar mitosis is responsible for chromosomal instability. Instead, Ganem et al. proposed that during bipolar cell division, cells with extra centrosomes can form transient multipolar intermediate structures, the geometry of which predisposes kinetochores to attach to microtubules that originate from different spindle poles (merotelic attachments). Although the extra centrosomes eventually cluster into two poles to form a functional bipolar spindle, some of the abnormally attached chromosomes persist and lag behind the normally attached chromosomes, increasing the probability of missegregation. In support of their hypothesis, the authors found that cells with extra centrosomes spent most of mitosis in a multipolar arrangement and had many merotelic attachments and lagging chromosomes.
Are extra centrosomes sufficient to promote chromosome missegregation during bipolar cell division? Ganem et al. generated tetraploid human BJ and RPE-1 cell lines by inhibiting cytokinesis with cytochalasin D and used fluorescence-activated cell sorting to isolate pure populations of tetraploid cells with two or more centrosomes at mitosis. They found that tetraploid cells with extra centrosomes had an increased rate of lagging chromosomes and chromosome missegregation compared with tetraploid cells with a normal complement of centrosomes. This indicates that lagging chromosomes and chromosomal missegregation are caused by the presence of extra centrosomes rather than a duplicated genome.
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