Department of Biochemistry and Biophysics, Graduate Program in Biochemistry and Molecular Biophysics, and Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Essays Biochem. 2019 Apr 23;63(1):15-27. doi: 10.1042/EBC20180060.
Proper segregation of chromosomes is an essential component of cell division. The centromere is the locus at which the kinetochore-the proteinaceous complex that ties chromosomes to microtubules-forms during mitosis and meiosis. Thus, the centromere is critical for equal segregation of chromosomes. The centromere is characterized by both protein and DNA elements: the histone H3 variant CENP-A epigenetically defines the location of the centromere while centromeric DNA sequences are neither necessary nor sufficient for centromere function. Paradoxically, the DNA sequences play a critical role in new centromere formation. In this essay, we discuss the contribution of both epigenetics and genetics at the centromere. Understanding these contributions is vital to efforts to control centromere formation on synthetic/artificial chromosomes and centromere strength on natural ones.
正确的染色体分离是细胞分裂的一个重要组成部分。着丝粒是动粒——将染色体与微管连接的蛋白质复合物——在有丝分裂和减数分裂过程中形成的位置。因此,着丝粒对于染色体的均等分离至关重要。着丝粒的特征既有蛋白质成分,也有 DNA 成分:组蛋白 H3 变体 CENP-A 在外层遗传上定义了着丝粒的位置,而着丝粒 DNA 序列对于着丝粒功能既不是必需的,也不是充分的。矛盾的是,DNA 序列在新着丝粒的形成中起着关键作用。在这篇文章中,我们讨论了着丝粒的表观遗传学和遗传学贡献。了解这些贡献对于控制合成/人工染色体上的着丝粒形成和自然染色体上的着丝粒强度的努力至关重要。