Centromeres are essential components of all eukaryotic chromosomes, including artificial/synthetic ones built in the laboratory. In humans, centromeres are typically located on repetitive α-satellite DNA, and these sequences are the "major ingredient" in first-generation human artificial chromosomes (HACs). Repetitive centromeric sequences present a major challenge for the design of synthetic mammalian chromosomes because they are difficult to synthesize, assemble, and characterize. Additionally, in most eukaryotes, centromeres are defined epigenetically. Here, we review the role of the genetic and epigenetic contributions to establishing centromere identity, highlighting recent work to hijack the epigenetic machinery to initiate centromere identity on a new generation of HACs built without α-satellite DNA. We also discuss the opportunities and challenges in developing useful unique sequence-based HACs.

中文翻译：

---

人类人工染色体的独特类型：无需重复的着丝粒DNA。

着丝粒是所有真核染色体的重要组成部分，包括在实验室中构建的人工/合成染色体。在人类中，着丝粒通常位于重复的α-卫星DNA上，这些序列是第一代人类人工染色体（HAC）中的“主要成分”。重复着丝粒序列对合成哺乳动物染色体的设计提出了主要挑战，因为它们难以合成，组装和表征。另外，在大多数真核生物中，着丝粒是表观遗传的。在这里，我们回顾了遗传和表观遗传贡献在建立着丝粒身份方面的作用，重点介绍了劫持表观遗传机制以在没有α-卫星DNA的新一代HAC上启动着丝粒身份的最新工作。