研究人员描述了与重组在α-卫星DNA上的CENP-A核小体(CENP-ANuc)结合的人类内动粒CCAN(Constitutive Centromere Associated Network)复合物的冷冻电镜结构。CCAN与CENP-ANuc形成边缘接触,而α-卫星重复的连接DNA片段从核小体完全包裹的一端出现,穿过紧紧抓住DNA的中央CENP-LN通道。CENP-TWSX活塞折叠模块进一步增强了DNA的结合,并以一种让人联想到典型核小体的方式部分包裹了连接DNA。
这项研究表明,CCAN对连接DNA的拓扑包裹提供了一种强有力的机制,通过这种机制,动粒可以承受有丝分裂纺锤体施加的推力和拉力。
据介绍,动粒组装在专门的着丝粒CENP-ANuc上,以介导染色体和有丝分裂纺锤体之间的连接。
附:英文原文
Title: Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome
Author: Stanislau Yatskevich, Kyle W. Muir, Dom Bellini, Ziguo Zhang, Jing Yang, Thomas Tischer, Masa Predin, Tom Dendooven, Stephen H. McLaughlin, David Barford
Issue&Volume: 2022-04-14
Abstract: Kinetochores assemble onto specialized centromeric CENP-A nucleosomes (CENP-ANuc) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-EM structures of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-ANuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, while a linker DNA segment of the α-satellite repeat emerges from the fully-wrapped end of the nucleosome to thread through the central CENP-LN channel that tightly grips the DNA. The CENP-TWSX histone-fold module further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the linker DNA by CCAN provides a robust mechanism by which kinetochores withstand both pushing and pulling forces exerted by the mitotic spindle.
DOI: abn3810
Source: https://www.science.org/doi/10.1126/science.abn3810