Structural insights into human CCAN complex assembled onto DNA.
Structural insights into human CCAN complex assembled onto DNA.
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对组装到 DNA 上的人类 CCAN 复合物的结构见解。
DOI：
10.1038/s41421-022-00439-6
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发表时间：
2022-09-09
期刊：
影响因子：
33.5
通讯作者：
Yao, Xuebiao
中科院分区：
文献类型：
--
作者：
Tian, Tian;Chen, Lili;Dou, Zhen;Yang, Zhisen;Gao, Xinjiao;Yuan, Xiao;Wang, Chengliang;Liu, Ran;Shen, Zuojun;Gui, Ping;Teng, Maikun;Meng, Xianlei;Hill, Donald L.;Li, Lin;Zhang, Xuan;Liu, Xing;Sun, Linfeng;Zang, Jianye;Yao, Xuebiao
在有丝分裂中，精确的染色体分离依赖于连接着丝粒染色质和纺锤体微管的动粒。芽殖酵母的着丝粒相对简单，通过着丝粒组成型着丝粒相关网络（CCAN）与单个微管相连。然而，人类染色体的复杂着丝粒包含数百万个DNA碱基对，并附着在多个微管上。在这里，通过使用冷冻电子显微镜和功能分析，我们揭示了人类CCAN如何与双链体DNA相互作用并促进准确的染色体分离的分子基础。整体结构涉及CCAN的组成子复合体的合作相互作用和相互依赖性。双链体DNA被人CCAN拓扑地捕获。此外，CENP-N不与CENP-A的RG环结合，而是与CCAN复合物中的DNA结合。DNA结合活性是CENP-LN定位于着丝粒和有丝分裂过程中染色体分离所必需的。因此，这些分析提供了新的见解，潜在的动粒组装和有丝分裂中的功能的行动机制。
In mitosis, accurate chromosome segregation depends on kinetochores that connect centromeric chromatin to spindle microtubules. The centromeres of budding yeast, which are relatively simple, are connected to individual microtubules via a kinetochore constitutive centromere associated network (CCAN). However, the complex centromeres of human chromosomes comprise millions of DNA base pairs and attach to multiple microtubules. Here, by use of cryo-electron microscopy and functional analyses, we reveal the molecular basis of how human CCAN interacts with duplex DNA and facilitates accurate chromosome segregation. The overall structure relates to the cooperative interactions and interdependency of the constituent sub-complexes of the CCAN. The duplex DNA is topologically entrapped by human CCAN. Further, CENP-N does not bind to the RG-loop of CENP-A but to DNA in the CCAN complex. The DNA binding activity is essential for CENP-LN localization to centromere and chromosome segregation during mitosis. Thus, these analyses provide new insights into mechanisms of action underlying kinetochore assembly and function in mitosis.
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影响因子：
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作者：
Kucukelbir, Alp;Sigworth, Fred J.;Tagare, Hemant D.
通讯作者：
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影响因子：
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