CENPs
At each mitosis, accurate segregation of every chromosome is ensured by the assembly of a kinetochore at each centromeric locus.
Six foundation kinetochore proteins that assemble hierarchically and co-dependently have been identified in vertebrates. CENP-A, Mis12, CENP-C, CENP-H and CENP-I localize to a core domain of centromeric chromatin. The sixth protein, CENP-B, although not essential in higher eukaryotes, has homologues in fission yeast that bind pericentric DNA and are essential for heterochromatin formation.
Foundation kinetochore proteins have various roles and mutual interactions, and their associations with centromeric DNA and heterochromatin create structural domains that support the different functions of the centromere.
Structure
Electron microscopy has revealed striking structural orderliness in kinetochore proteins and protein complexes that associate with microtubules. In addition to their astonishing appearance and intrinsic beauty, the structures are functionally informative.
The Dam1 and Ndc80 complexes bind to the microtubule lattice as rings and chevrons, respectively. These structures give insight into how the kinetochore couples to dynamic microtubules, a process crucial to the accurate segregation of chromosomes.
HURP and kinesin-13 arrange tubulin into sleeves and bracelets surrounding the microtubule lattice. These structures might reflect the ability of these proteins to modulate microtubule dynamics by interacting with specialized tubulin configurations.
Members
| CENPA | CENPB | CENPC |
References
Davis TN, Wordeman L. Rings, bracelets, sleeves, and chevrons: new structures of kinetochore proteins. Trends Cell Biol. 2007 Aug;17(8):377-82. PMID: #17766118#