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Human artificial chromosome: Chromatin assembly mechanisms and CENP-B.
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-02-07 , DOI: 10.1016/j.yexcr.2020.111900
Jun-Ichirou Ohzeki 1 , Koichiro Otake 1 , Hiroshi Masumoto 1
Affiliation  

The centromere is a specialized chromosomal locus required for accurate chromosome segregation. Heterochromatin also assembles around centromere chromatin and forms a base that supports sister chromatid cohesion until anaphase begins. Both centromere chromatin and heterochromatin assemble on a centromeric DNA sequence, a highly repetitive sequence called alphoid DNA (α-satellite DNA) in humans. Alphoid DNA can form a de novo centromere and subsequent human artificial chromosome (HAC) when introduced into the human culture cells HT1080. HAC is maintained stably as a single chromosome independent of other human chromosomes. For de novo centromere assembly and HAC formation, the centromere protein CENP-B and its binding sites, CENP-B boxes, are required in the repeating units of alphoid DNA. CENP-B has multiple roles in de novo centromere chromatin assembly and stabilization and in heterochromatin formation upon alphoid DNA introduction into the cells. Here we review recent progress in human artificial chromosome construction and centromere/heterochromatin assembly and maintenance, focusing on the involvement of human centromere DNA and CENP-B protein.

中文翻译:

人类人工染色体:染色质组装机制和CENP-B。

着丝粒是精确的染色体分离所需的专门的染色体位点。异染色质还在着丝粒染色质周围聚集,形成支持姐妹染色单体凝聚的基础,直到后期开始。着丝粒染色质和异染色质都装配在着丝粒DNA序列上,着丝粒DNA序列是人类中高度重复的序列,称为Alphoid DNA(α-卫星DNA)。引入人类培养细胞HT1080中时,脂质DNA可以形成新生中心和随后的人类人工染色体(HAC)。HAC作为独立于其他人类染色体的单个染色体稳定维持。对于从头着丝粒组装和HAC形成,着丝粒蛋白CENP-B及其结合位点CENP-B盒在alphaid DNA的重复单元中是必需的。CENP-B在从头着丝粒染色质组装和稳定以及将脂质体DNA引入细胞后异染色质的形成中具有多种作用。在这里,我们回顾了人类人工染色体构建和着丝粒/异染色质组装和维护的最新进展,重点是人类着丝粒DNA和CENP-B蛋白的参与。
更新日期:2020-02-10
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