Chromosome transmission in S. cerevisiae requires the activities of many structural and regulatory proteins required for the replication, repair, recombination and segregation of chromosomal DNA, and co-ordination of the chromosome cycle with progression through cell cycle. An important structural domain on each chromosome is the kinetochore (centromere DNA and associated proteins), which provides the site of attachment of chromosomes to the spindle microtubules. Stoler et al. have recently reported the cloning of an essential gene CSE4, mutations in which cause chromosome nondisjunction of a marked chromosome bearing a centromere DNA mutation. The cse4-1 mutation causes cells to arrest in the G2/M phase of the cell cycle with a 2N DNA content in a RAD9 checkpoint-independent manner. The carboxyl terminus of Cse4p and the human centromere-localized protein CENP-A have a high degree of homology to the C-terminal domain of histone H3. Since both CENP-A and Cse4p also have biochemical properties similar to histones H3 and H4, it is tempting to speculate that these histone H3-like proteins are components of specialized nucleosomes, a class of which may be unique to the centromeres.