The centromere is a specialized chromosomal structure essential for chromosome segregation. Centromere dysfunction leads to chromosome segregation errors and genome instability. In most eukaryotes, centromere identity is specified epigenetically by CENP-A, a centromere-specific histone H3 variant. CENP-A replaces histone H3 in centromeres, and nucleates the assembly of the kinetochore complex. Mislocalization of CENP-A to non-centromeric regions causes ectopic assembly of CENP-A chromatin, which has a devastating impact on chromosome segregation and has been linked to a variety of human cancers. How non-centromeric regions are protected from CENP-A misincorporation in normal cells is largely unexplored. Here, we review the most recent advances on the mechanisms underlying the prevention of ectopic centromere formation, and discuss the implications in human disease.

着丝粒是染色体分离所必需的特殊染色体结构。着丝粒功能障碍导致染色体分离错误和基因组不稳定。在大多数真核生物中，着丝粒身份由 CENP-A（一种着丝粒特异性组蛋白 H3 变体）表观遗传指定。CENP-A 取代着丝粒中的组蛋白 H3，并使着丝粒复合体的组装成核。CENP-A 错误定位到非着丝粒区域会导致 CENP-A 染色质异位组装，这对染色体分离具有破坏性影响，并与多种人类癌症有关。非着丝粒区域如何在正常细胞中免受 CENP-A 错误掺入的影响在很大程度上尚未得到探索。在这里，我们回顾了预防异位着丝粒形成的机制的最新进展，