Nature Cell Biology 8, 446 - 457 (2006)
Published online: 16 April 2006; | doi:10.1038/ncb1396
The CENP-H–I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeresMasahiro Okada1, Iain M. Cheeseman2, Tetsuya Hori1, Katsuya Okawa3, Ian X. McLeod4, John R. Yates III4, Arshad Desai2
& Tatsuo Fukagawa11
Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Shizuoka 411–8540, Japan. 2
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA. 3
HMRO, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. 4
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Correspondence should be addressed to Tatsuo Fukagawa tfukagaw@lab.nig.ac.jp 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.
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