CENPA

CENP-A, or centromere protein A, is a histone H3 variant encoded by the CENPA gene. It replaces conventional histone H3 in centromeric nucleosomes and serves as a core epigenetic determinant of centromere identity, guiding the assembly of the kinetochore, the protein structure that mediates chromosome attachment to the spindle during cell division. In many eukaryotes, centromeric identity is largely specified by the presence of CENP-A rather than by DNA sequence alone.

CENP-A deposition at centromeres is tightly regulated in the cell cycle. In human cells, the histone chaperone HJURP, along with the Mis18 complex, facilitates targeted CENP-A assembly mainly during late mitosis and early G1, helping to replenish centromeric nucleosomes after DNA replication. The CENP-A nucleosome is a component of the constitutive centromere-associated network (CCAN) and contributes to recruiting outer kinetochore proteins that enable proper kinetochore maturation and spindle attachment.

Across eukaryotes, CENP-A is highly conserved but can show organism-specific variations in its N-terminal tail and neighboring centromeric proteins. Its presence marks functional centromeres and influences centromere stability and fidelity of chromosome segregation.

Dysregulation of CENP-A is associated with chromosome instability and aneuploidy in cancer. Overexpression or mislocalization of CENP-A can promote abnormal kinetochore formation and has been observed in various tumor contexts, making CENP-A a focus of research on genome maintenance and oncogenesis.