Figure 3. Hypothetical mechanisms by which aberrant centrosome dynamics promote merotely and chromosome lagging.

Normal centrosome dynamics promote amphitelic attachments and faithful chromosome segregation between daughter cells. Delayed centrosome disengagement promotes merotelic attachments in early prometaphase because kinetochores are accessible to microtubules from spindle poles in close proximity. At this stage, immature kinetochores have not yet recruited all of the proteins necessary for proper kinetochore-microtubule attachments, increasing the likelihood of merotelic attachments and/or decreasing the efficiency at which merotelic attachments are detected and resolved. Alternatively, delayed centrosome disengagement is associated with spindle asymmetry in metaphase, which may also promote misattachments prior to anaphase. Accelerated centrosome disengagement may promote merotelic attachments in early prometaphase again through a combination of suboptimal microtubule approach angle to the kinetochore and immature kinetochores that cannot detect and/or resolve merotelic attachments. Like delayed disengagement, accelerated centrosome disengagement has been associated with spindle asymmetry in metaphase, which is likely to promote merotelic attachments just prior to anaphase onset. Unresolved merotelic attachments resolve in chromosome lagging. MT; microtubule. KT; kinetochore.