Figure 2.

A catastrophic fate for centromere-inactivated Y chromosomes. Following centromere inactivation using the CENP-A replacement strategy, the Y chromosome fails to properly congress during metaphase and subsequently missegregates in anaphase to produce aneuploid daughter cells with loss, gains, or micronucleation of the Y chromosome. When sequestered in a micronucleus, the Y chromosome undergoes extensive fragmentation in the next mitosis. The resulting fragments incorporate back into the nucleus for subsequent re-ligation by classical non-homologous end joining during interphase.