The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres
The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres
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DOI：
10.1038/ncb1396
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发表时间：
2006-05-01
影响因子：
21.3
通讯作者：
Fukagawa, T
中科院分区：
文献类型：
--
作者：
Okada, M;Cheeseman, IM;Fukagawa, T
在脊椎动物中，着丝粒缺乏确定的序列，并且被认为是通过表观遗传机制繁殖的，所述表观遗传机制涉及包含组蛋白H3变体着丝粒蛋白（CENP）-A的特化核小体的掺入。然而，CENP-A靶向着丝粒的确切机制仍然知之甚少。在这里，我们从人类和鸡细胞中分离出一种多亚基复合物，其中包括已建立的内部动粒组分CENP-H和CENP-I以及其他九种蛋白质。我们对这些蛋白质的分析表明，CENP-H-I复合物可以分为三个功能性子复合物，每个子复合物都是忠实的染色体分离所需的。有趣的是，在CENP-H-I复合物蛋白的一个亚类的敲除突变体中，新表达的CENP-A不能有效地掺入着丝粒中，这表明CENP-H-I复合物可能部分地作为指导CENP-A沉积到着丝粒的标记物起作用。
In vertebrates, centromeres lack defined sequences and are thought to be propagated by epigenetic mechanisms involving the incorporation of specialized nucleosomes containing the histone H3 variant centromere protein (CENP)-A. However, the precise mechanisms that target CENP-A to centromeres remain poorly understood. Here, we isolated a multi-subunit complex, which includes the established inner kinetochore components CENP-H and CENP-I, and nine other proteins, from both human and chicken cells. Our analysis of these proteins demonstrates that the CENP-H-I complex can be divided into three functional sub-complexes, each of which is required for faithful chromosome segregation. Interestingly, newly expressed CENP-A is not efficiently incorporated into centromeres in knockout mutants of a subclass of CENP-H-I complex proteins, indicating that the CENP-H-I complex may function, in part, as a marker directing CENP-A deposition to centromeres.