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The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres
Nature Cell Biology DOI 10.1038/Ncb1396
Fukagawa Laboratory, Division of Molecular Genetics
The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres
Okada, M., Cheeseman, I.M., Hori, T., Okawa, K., McLeod, I.X., Yates, J.R. III, Desai, A., and Fukagawa, T.
Nature Cell Biology, DOI: 10.1038/Ncb1396 (2006)

  Chromosome segregation in eukaryotes requires a multi-protein structure termed the kinetochore, which assembles on centromeric DNA to mediate the binding of spindle microtubules to chromosomes and chromosome movement. 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 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 9 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 mark directing CENP-A deposition to centromeres.

Model of a mechanism for newly synthesized CENP-A loading into centromeres. After chromosome replication, half of the existing CENP-A nucleosomes remain at the centromere of each newly replicated sister chromatid together with associated the CENP-H-I complex. For nascent CENP-A deposition, the CENP-H-I complex recruits a putative CENP-A loading factor and facilitates targeting of CENP-A into centromeric chromatin. Thus, the CENP-H-I complex may function as a marker for CENP-A incorporation.