Each S. cerevisiae chromosome contains a single centromere that is necessary and sufficient for accurate chromosomal segregation during mitosis and meiosis (2). In S. cerevisiae, each of the sixteen centromeres (CEN1-CEN16) is approximately 125 base pairs (bp) long and can be subdivided into three consensus elements: CDEI, CDEII, and CDEIII. CDEI and CDEIII are 8 bp and 26 bp imperfect palindromes, respectively, while CDEII is an AT-rich sequence of 78-86 bp that lies between CDEI and CDEIII (reviewed in 3). CDEII and CDEIII are essential for centromere function (4, 5). In contrast to the compact organization of the S. cerevisiae centromere, centromeres in S. pombe and higher eukaryotes are much larger (40-100 kb for S. pombe and several Mb for humans) and contain a variety of repetitive elements.

The centromeric region of the chromosome is the site that mediates assembly of the kinetochore, a multiprotein structure consisting of at least 8 protein complexes, to which spindle microtubules attach to facilitate chromosome segregation during mitosis and meiosis. Kinetochore assembly is thought to occur in three layers, called the inner, central, and outer layers, as interactions among some complexes exhibit a hierarchical interdependence (reviewed in 6). Assembly begins with the interaction of inner centromere binding proteins that directly bind to centromeric DNA. The essential CBF3 complex, consisting of Cep3p, Cbf2p/Ndc10p, Ctf13p, and Skp1p, binds to CDEIII; this interaction may function to nucleate kinetochore assembly (7). Cbf2p/Ndc10p alone binds to CDEII over a region of 80 base pairs, suggesting that a multimeric structure is formed (8). The non-essential Cbf1p homodimer binds to CDEI and induces DNA bending, which is thought to be important for stabilizing kinetochore structure (9). Mif2p also likely interacts directly with the centromeric DNA, although it is not yet entirely clear where it binds (10, 7). Cse4p is likely a component of a specialized centromeric nucleosome (11). The additional central and outer kinetochore complexes then assemble onto the inner layer to form a functional kinetochore.

For detailed models showing kinetochore assembly, see Figure 6 of Meluh and Koshland, Figure 3 of McAinsh, et al., or Figure 6 of Espelin, et al. Click on the figure for a schematic diagram of the centromere and centromere binding proteins.

Last updated: 2004-10-11