Laboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, 292-0818, Japan.
Laboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, 292-0818, Japan.
Exp Cell Res. 2020 Apr 15;389(2):111900. doi: 10.1016/j.yexcr.2020.111900. Epub 2020 Feb 8.
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.
着丝粒是一种用于精确染色体分离的特殊染色体位置。异染色质也会围绕着丝粒染色质组装，并形成一个基础，支持姐妹染色单体的黏合，直到后期开始。着丝粒染色质和异染色质都组装在着丝粒 DNA 序列上，该序列是人类中高度重复的序列，称为α卫星 DNA（α-satellite DNA）。当将α卫星 DNA 引入人类培养细胞 HT1080 中时，它可以形成新的着丝粒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。对于新的着丝粒组装和 HAC 形成，在α卫星 DNA 的重复单元中需要着丝粒蛋白 CENP-B 及其结合位点 CENP-B 盒。CENP-B 在新的着丝粒染色质组装和稳定以及在将α卫星 DNA 引入细胞时异染色质形成中具有多种作用。在这里，我们综述了人类人工染色体构建和着丝粒/异染色质组装和维持的最新进展，重点介绍了人类着丝粒 DNA 和 CENP-B 蛋白的参与。
