Bloom Kerry, Costanzo Vincenzo
Department of Biology, University of North Carolina at Chapel Hill, 623 Fordham Hall CB#3280, Chapel Hill, NC, 27599-3280, USA.
DNA Metabolism Laboratory, IFOM, The FIRC Institute of Molecular Oncology, Vai Adamello 16, 21139, Milan, Italy.
Prog Mol Subcell Biol. 2017;56:515-539. doi: 10.1007/978-3-319-58592-5_21.
The centromere is the genetic locus that specifies the site of kinetochore assembly, where the chromosome will attach to the kinetochore microtubule. The pericentromere is the physical region responsible for the geometry of bi-oriented sister kinetochores in metaphase. In budding yeast the 125 bp point centromere is sufficient to specify kinetochore assembly. The flanking region is enriched (3X) in cohesin and condensin relative to the remaining chromosome arms. The enrichment spans about 30-50 kb around each centromere. We refer to the flanking chromatin as the pericentromere in yeast. In mammals, a 5-10 Mb region dictates where the kinetochore is built. The kinetochore interacts with a very small fraction of DNA on the surface of the centromeric region. The remainder of the centromere lies between the sister kinetochores. This is typically called centromere chromatin. The chromatin sites that directly interface to microtubules cannot be identified due to the repeated sequence within the mammalian centromere. However in both yeast and mammals, the total amount of DNA between the sites of microtubule attachment in metaphase is highly conserved. In yeast the 16 chromosomes are clustered into a 250 nm diameter region, and 800 kb (16 × 50 kb) or ~1 Mb of DNA lies between sister kinetochores. In mammals, 5-10 Mb lies between sister kinetochores. In both organisms the sister kinetochores are separated by about 1 μm. Thus, centromeres of different organisms differ in how they specify kinetochore assembly, but there may be important centromere chromatin functions that are conserved throughout phylogeny. Recently, centromeric chromatin has been reconstituted in vitro using alpha satellite DNA revealing unexpected features of centromeric DNA organization, replication, and response to stress. We will focus on the conserved features of centromere in this review.
着丝粒是指定动粒组装位点的基因座，染色体将在此处附着于动粒微管。着丝粒周围区域是负责中期双定向姐妹动粒几何形状的物理区域。在芽殖酵母中，125 bp的点着丝粒足以指定动粒组装。相对于其余染色体臂，侧翼区域的黏连蛋白和凝聚素富集（3倍）。这种富集在每个着丝粒周围延伸约30 - 50 kb。我们将酵母中的侧翼染色质称为着丝粒周围区域。在哺乳动物中，一个5 - 10 Mb的区域决定了动粒的构建位置。动粒与着丝粒区域表面的一小部分DNA相互作用。着丝粒的其余部分位于姐妹动粒之间。这通常被称为着丝粒染色质。由于哺乳动物着丝粒内的重复序列，无法确定直接与微管接触的染色质位点。然而，在酵母和哺乳动物中，中期微管附着位点之间的DNA总量高度保守。在酵母中，16条染色体聚集在一个直径250 nm的区域内，姐妹动粒之间有800 kb（16×50 kb）或约1 Mb的DNA。在哺乳动物中，姐妹动粒之间有5 - 10 Mb。在这两种生物中，姐妹动粒之间的距离约为1μm。因此，不同生物体的着丝粒在指定动粒组装的方式上有所不同，但可能存在贯穿系统发育过程保守的重要着丝粒染色质功能。最近，使用α卫星DNA在体外重建了着丝粒染色质，揭示了着丝粒DNA组织、复制和应激反应的意外特征。在本综述中，我们将重点关注着丝粒的保守特征。
