Figure 2

Transient defects of mitotic spindle geometry and chromosome mis-segregation. A. Transient multipolarity mechanism, in which initial assembly of a multipolar spindle (first panel) favors the formation of merotelic kinetochore attachment (second panel). Subsequently, centrosome clustering/coalescence leads to mitotic spindle bipolarization (third panel). However, merotelic kinetochore attachment can persist into anaphase and produce a chromosome segregation defect in the form of an anaphase lagging chromosome (fourth panel). B. Incomplete spindle pole separation at NEB results in a transient spindle geometry defect that promotes formation of kinetochore mis-attachments. If the centrosomes are very close to one another (top row), chromosomes are extremely likely to form syntelic attachments (first panel), which can be converted into merotelic attachments upon spindle bipolarization (second panel). If the centrosomes are not completely separated, but more than a few microns apart (bottom row), merotelic attachments can form directly without transitioning through a syntelic intermediate (first and second panel). In both cases, merotelic attachments can persist through mitosis (third panels) and induce chromosome mis-segregation in the form of anaphase lagging chromosomes (fourth panels). Adapted from [57].