Recent insights into mechanisms preventing ectopic centromere formation.

Recent insights into mechanisms preventing ectopic centromere formation.
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DOI:
10.1098/rsob.210189
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发表时间:
2021-09
期刊:
影响因子:
5.8
通讯作者:
Li F
Li F
中科院分区:
生物学2区
文献类型:
--
作者:
Dong Q;Yang J;Gao J;Li F

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着丝粒是染色体分离所必需的一种特殊的染色体结构。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,着丝粒的同一性是由着丝粒特异性组蛋白H3变异体CENP-A表观遗传决定的。CENP-A取代着丝粒中的组蛋白H3,并使着丝粒复合体组装成核。CENP-A在非着丝粒区域的错误定位导致CENP-A染色质的异位组装,这对染色体分离具有破坏性影响,并与多种人类癌症有关。在正常细胞中,如何保护非着丝粒区域免受CENP-A错掺入在很大程度上是未知的。在这里,我们回顾了有关预防异位着丝粒形成机制的最新进展,并讨论了其在人类疾病中的意义。
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.
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