Figure 1.

Heterogeneity in centromere composition impacts chromosome segregation fidelity during mitosis. Centromere DNA (alpha-satellite and CENP-B boxes) and the abundance of CENtromere Proteins (CENP-A, CENP-B, CENP-C) vary between chromosomes (inter-chromosome variability A/B vs C/D) and also between homologs (intra-chromosome variability, A and B). During prophase, kinetochore (KT) proteins are recruited at the centromeres to mediate the attachment of the microtubules. During metaphase, correctly attached chromosomes are aligned to the metaphase plate, while bigger chromosomes harboring a small centromere (A) can be mis-aligned following mitotic perturbation. Sister chromatids are then separated and pulled apart to the opposite poles of the cell during anaphase, and at mitotic exit, the nuclear membrane is reformed to give rise to two daughter cells. The mis-aligned chromosome bearing a “smaller” centromere (A) was not equally separated and could be encapsulated into a micronucleus, giving rise to aneuploidy in one of the two daughter cells.