Replicated chromosomes include two kinetochores that control chromosome segregation during mitosis. Centromere Protein-A (CENP-A), a histone H3-like protein, contains a C-terminal H3-like domain which is required for centromere localization of CENP-A. It is essential for kinetochore targeting of CENP-C. In the presence of DNA, CENP-A forms an octameric complex with histones H2A, H2B, and H4. CENP-A specifically localizes to active centromeres and is a component of specialized centromeric nucleosomes on which kinetochores are assembled. CENP-A is essential for nucleosomal packaging of centromeric DNA at interphase and functions as a centromere formation marker on chromosomes.