Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Chromosome Res. 2012 Jul;20(5):607-19. doi: 10.1007/s10577-012-9296-x.
Neocentromeres are ectopic sites where new functional kinetochores assemble and permit chromosome segregation. Neocentromeres usually form following genomic alterations that remove or disrupt centromere function. The ability to form neocentromeres is conserved in eukaryotes ranging from fungi to mammals. Neocentromeres that rescue chromosome fragments in cells with gross chromosomal rearrangements are found in several types of human cancers, and in patients with developmental disabilities. In this review, we discuss the importance of neocentromeres to human health and evaluate recently developed model systems to study neocentromere formation, maintenance, and function in chromosome segregation. Additionally, studies of neocentromeres provide insight into native centromeres; analysis of neocentromeres found in human clinical samples and induced in model organisms distinguishes features of centromeres that are dependent on centromere DNA from features that are epigenetically inherited together with the formation of a functional kinetochore.
新着丝粒是异位点,在这些位点上可以组装新的有功能的动粒,并允许染色体分离。新着丝粒通常在去除或破坏着丝粒功能的基因组改变后形成。从真菌到哺乳动物等真核生物都具有形成新着丝粒的能力。在有严重染色体重排的细胞中,能够拯救染色体片段的新着丝粒存在于几种类型的人类癌症和发育障碍患者中。在这篇综述中,我们讨论了新着丝粒对人类健康的重要性,并评估了最近开发的模型系统,以研究染色体分离中新着丝粒的形成、维持和功能。此外,新着丝粒的研究为了解天然着丝粒提供了线索;对人类临床样本中发现的新着丝粒和在模型生物中诱导的新着丝粒的分析,区分了依赖于着丝粒 DNA 的着丝粒特征和与功能性动粒形成一起遗传的表观遗传特征。