Jagannathan Madhav, Yamashita Yukiko M
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109.
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109.
Cold Spring Harb Symp Quant Biol. 2017;82:319-327. doi: 10.1101/sqb.2017.82.034504. Epub 2018 Apr 2.
Satellite DNAs are simple tandem repeats that exist at centromeric and pericentromeric regions on eukaryotic chromosomes. Unlike the centromeric satellite DNA that comprises the vast majority of natural centromeres, function(s) for the much more abundant pericentromeric satellite repeats are poorly understood. In fact, the lack of coding potential allied with rapid divergence of repeat sequences across eukaryotes has led to their dismissal as "junk DNA" or "selfish parasites." Although implicated in various biological processes, a conserved function for pericentromeric satellite DNA remains unidentified. We have addressed the role of satellite DNA through studying chromocenters, a cytological aggregation of pericentromeric satellite DNA from multiple chromosomes into DNA-dense nuclear foci. We have shown that multivalent satellite DNA-binding proteins cross-link pericentromeric satellite DNA on chromosomes into chromocenters. Disruption of chromocenters results in the formation of micronuclei, which arise by budding off the nucleus during interphase. We propose a model that satellite DNAs are critical chromosome elements that are recognized by satellite DNA-binding proteins and incorporated into chromocenters. We suggest that chromocenters function to preserve the entire chromosomal complement in a single nucleus, a fundamental and unquestioned feature of eukaryotic genomes. We speculate that the rapid divergence of satellite DNA sequences between closely related species results in discordant chromocenter function and may underlie speciation and hybrid incompatibility.
卫星DNA是存在于真核生物染色体着丝粒和着丝粒周围区域的简单串联重复序列。与构成绝大多数天然着丝粒的着丝粒卫星DNA不同,人们对数量多得多的着丝粒周围卫星重复序列的功能了解甚少。事实上,由于缺乏编码潜力以及真核生物中重复序列的快速分化,它们被视为“垃圾DNA”或“自私的寄生虫”而被摒弃。尽管着丝粒周围卫星DNA与各种生物学过程有关,但其保守功能仍未明确。我们通过研究染色中心来探讨卫星DNA的作用,染色中心是来自多条染色体的着丝粒周围卫星DNA在细胞核中聚集形成的DNA密集区。我们发现多价卫星DNA结合蛋白将染色体上的着丝粒周围卫星DNA交联形成染色中心。染色中心的破坏会导致微核的形成,微核是在间期从细胞核中出芽产生的。我们提出一个模型,即卫星DNA是关键的染色体元件,被卫星DNA结合蛋白识别并整合到染色中心。我们认为染色中心的功能是在单个细胞核中保存整个染色体组,这是真核生物基因组的一个基本且毋庸置疑的特征。我们推测,密切相关物种之间卫星DNA序列的快速分化会导致染色中心功能失调,这可能是物种形成和杂种不亲和的基础。