CCAN Makes Multiple Contacts with Centromeric DNA to Provide Distinct Pathways to the Outer Kinetochore
CCAN Makes Multiple Contacts with Centromeric DNA to Provide Distinct Pathways to the Outer Kinetochore
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DOI：
10.1016/j.cell.2008.10.019
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发表时间：
2008-12-12
期刊：
影响因子：
64.5
通讯作者：
Fukagawa, Tatsuo
中科院分区：
文献类型：
--
作者：
Hori, Tetsuya;Amano, Miho;Fukagawa, Tatsuo
动粒的特化和组装需要在着丝粒处有针对性地沉积含有组蛋白H3变体CENP - A的特殊核小体。然而，CENP - A并不足以驱动完整的动粒组装，而且着丝粒染色质是如何形成的也不清楚。在此，我们确定CENP - W是蛋白质的近DNA组成型着丝粒相关网络（CCAN）的一个组分。我们证明CENP - W与CCAN组分CENP - T一起形成一个DNA结合复合物。该复合物在着丝粒区域直接与核小体DNA以及经典组蛋白H3结合，但不与CENP - A结合。除了另一种假定的DNA结合蛋白CENP - C外，CENP - T/CENP - W在其他CCAN组分的上游发挥作用。我们的分析表明，CENP - T/CENP - W和CENP - C提供了不同的途径将着丝粒与外动粒组装连接起来。总之，我们的研究结果表明，CENP - T/CENP - W复合物与CENP - A协同直接参与着丝粒染色质结构的建立。
Kinetochore specification and assembly requires the targeted deposition of specialized nucleosomes containing the histone H3 variant CENP-A at centromeres. However, CENP-A is not sufficient to drive full-kinetochore assembly, and it is not clear how centromeric chromatin is established. Here, we identify CENP-W as a component of the DNA-proximal constitutive centromere-associated network (CCAN) of proteins. We demonstrate that CENP-W forms a DNA-binding complex together with the CCAN component CENP-T. This complex directly associates with nucleosomal DNA and with canonical histone H3, but not with CENP-A, in centromeric regions. CENP-T/CENP-W functions upstream of other CCAN components with the exception of CENP-C, an additional putative DNA-binding protein. Our analysis indicates that CENP-T/CENP-W and CENP-C provide distinct pathways to connect the centromere with outer kinetochore assembly. In total, our results suggest that the CENP-T/CENP-W complex is directly involved in establishment of centromere chromatin structure coordinately with CENP-A.