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The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle.
Open Biology ( IF 5.8 ) Pub Date : 2020-06-10 , DOI: 10.1098/rsob.200051
Kathryn Kixmoeller 1, 2, 3, 4 , Praveen Kumar Allu 1, 2, 3 , Ben E Black 1, 2, 3, 4
Affiliation  

Eukaryotic chromosome segregation relies upon specific connections from DNA to the microtubule-based spindle that forms at cell division. The chromosomal locus that directs this process is the centromere, where a structure called the kinetochore forms upon entry into mitosis. Recent crystallography and single-particle electron microscopy have provided unprecedented high-resolution views of the molecular complexes involved in this process. The centromere is epigenetically specified by nucleosomes harbouring a histone H3 variant, CENP-A, and we review recent progress on how it differentiates centromeric chromatin from the rest of the chromosome, the biochemical pathway that mediates its assembly and how two non-histone components of the centromere specifically recognize CENP-A nucleosomes. The core centromeric nucleosome complex (CCNC) is required to recruit a 16-subunit complex termed the constitutive centromere associated network (CCAN), and we highlight recent structures reported of the budding yeast CCAN. Finally, the structures of multiple modular sub-complexes of the kinetochore have been solved at near-atomic resolution, providing insight into how connections are made to the CCAN on one end and to the spindle microtubules on the other. One can now build molecular models from the DNA through to the physical connections to microtubules.

中文翻译:

着丝粒成为焦点:从CENP-A核小体到与纺锤体的动粒连接。

真核染色体的分离依赖于DNA与细胞分裂时形成的基于微管的纺锤体之间的特定连接。指导这一过程的染色体位点是着丝粒,着丝粒在进入有丝分裂时就形成了一种叫做动粒体的结构。最近的晶体学和单粒子电子显微镜已经提供了此过程中涉及的分子复合物的前所未有的高分辨率视图。着丝粒是由携带组蛋白H3变体CENP-A的核小体表观遗传指定的,我们回顾了最近的研究进展,即如何将着丝粒染色质与染色体的其余部分区分开,介导其组装的生化途径以及两个非组蛋白组分的生化途径。着丝粒特异性识别CENP-A核小体。需要核心着丝粒核小体复合物(CCNC)来募集称为组成型着丝粒相关网络(CCAN)的16个亚基复合物,我们着重介绍了发芽酵母CCAN的最新结构。最终,以接近原子的分辨率解决了动粒的多个模块亚复合物的结构,从而提供了对如何在一端与CCAN以及在另一端与纺锤体微管进行连接的见解。现在,人们可以建立从DNA到与微管的物理连接的分子模型。提供有关如何在一端与CCAN以及在另一端与纺锤微管建立连接的见解。现在,人们可以建立从DNA到与微管的物理连接的分子模型。提供有关如何在一端与CCAN以及在另一端与纺锤微管建立连接的见解。现在,人们可以建立从DNA到与微管的物理连接的分子模型。
更新日期:2020-06-10
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