Perpelescu Marinela, Fukagawa Tatsuo
Department of Molecular Genetics, National Institute of Genetics and the Graduate University for Advanced Studies, Mishima, Shizuoka, Japan.
Chromosoma. 2011 Oct;120(5):425-46. doi: 10.1007/s00412-011-0330-0. Epub 2011 Jul 13.
Equal distribution of DNA in mitosis requires the assembly of a large proteinaceous ensemble onto the centromeric DNA, called the kinetochore. With few exceptions, kinetochore specification is independent of the DNA sequence and is determined epigenetically by deposition at the centromeric chromatin of special nucleosomes containing an H3-related histone, CENP-A. Onto centromeric CENP-A chromatin is assembled the so-called constitutive centromere-associated network (CCAN) of 16 proteins distributed in several functional groups as follows: CENP-C, CENP-H/CENP-I/CENP-K/, CENP-L/CENP-M/CENP-N, CENP-O/CENP-P/CENP-Q/CENP-R/CENP-U(50), CENP-T/CENP-W, and CENP-S/CENP-X. One role of the CCAN is to recruit outer kinetochore components further, such as KNL1, the Mis12 complex, and the Ndc80 complex (KMN network) to which attach the spindle microtubules with their structural and regulatory proteins. Among the CENPs in CCAN, CENP-C and CENP-T are required in parallel for operational kinetochore specification and spindle attachment. This review presents discussion of the latest structural and functional data on CENP-A and CENPs from the CCAN as well as their interaction with the KMN network.
有丝分裂过程中DNA的均匀分配需要在着丝粒DNA上组装一个大型蛋白质复合体，即动粒。除少数例外情况外，动粒的特化不依赖于DNA序列，而是通过在含有H3相关组蛋白CENP - A的特殊核小体的着丝粒染色质上沉积，由表观遗传决定。在着丝粒CENP - A染色质上组装了由16种蛋白质组成的所谓组成型着丝粒相关网络（CCAN），这些蛋白质分布在几个功能组中，如下所示：CENP - C、CENP - H/CENP - I/CENP - K、CENP - L/CENP - M/CENP - N、CENP - O/CENP - P/CENP - Q/CENP - R/CENP - U(50)、CENP - T/CENP - W以及CENP - S/CENP - X。CCAN的一个作用是进一步招募外动粒成分，如KNL1、Mis12复合体和Ndc80复合体（KMN网络），纺锤体微管及其结构和调节蛋白附着在这些复合体上。在CCAN中的CENP中，CENP - C和CENP - T对于功能性动粒特化和纺锤体附着是并行必需的。本综述讨论了来自CCAN的CENP - A和CENP的最新结构和功能数据，以及它们与KMN网络的相互作用。
