IDENTIFICATION OF BINDING PARTNERS FOR THE AMINO TERMINUS OF HUMAN CENP-A

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Centromeres direct the assembly of the proteinaceous structure called the kinetochore that mediates the interaction between chromosomes and spindle microtubules during mitosis. In order for sister chromosomes to be faithfully segregated to opposing daughter cells during cell division, each chromosome must possess a single centromere. The histone H3 variant CENP-A is thought to comprise part of the primary epigenetic mechanism by which centromeres are specified by forming a centromere-specific nucleosome. How CENP-A is specifically loaded into centromeres is not understood, nor is how CENP-A might direct the assembly of kinetochores. As mentioned, CENP-A is a histone H3 variant. It comprises a histone fold domain which shares a high degree of similarity with histone H3 (60%) and is required for nucleosome structure, winding DNA, and appropriately targeting CENP-A to the centromere. In contrast, the 42 amino acid N-terminal tail of CENP-A shares only limited amino acid similarity to histone H3, and no function has yet been assigned to this region. The amino termini of other histones have been shown to be sites of modification (acetylation, methylation, and phosphorylation) that have proven important for chromosomal structure and gene expression. It is our goal to identify binding partners that might lend insight into the function of CENP-A using TAP-tagged versions of the CENP-A expressed in HeLa cells.