Kinetochores enable the precise distribution of chromosomes during the eukaryotic cell division to avoid aneuploidy ( Santaguida and Musacchio, 2009) which is associated with tumorigenesis, congenital trisomies and aging ( Baker et al., 2005 Pfau and Amon, 2012). This study shows molecular characteristics of the point-centromere kinetochore architecture and suggests a role for the Ctf19 C-terminus in mediating CPC-binding and accurate chromosome segregation. Tethering Sli15 to Ame1/Okp1 rescued synthetic lethality upon Ctf19 depletion in a Sli15 centromere-targeting deficient mutant.
The Sli15/Ipl1 INCENP/Aurora-B core-CPC interacted with COMA in vitro through the Ctf19 C-terminus whose deletion affected chromosome segregation fidelity in Sli15 wild-type cells. By performing crosslink-guided in vitro reconstitution of budding yeast kinetochore complexes we showed that the Ame1/Okp1 CENP-U/Q heterodimer, which forms the COMA complex with Ctf19/Mcm21 CENP-P/O, selectively bound Cse4 CENP-A nucleosomes through the Cse4 N-terminus. The inner kinetochore is assembled on CENP-A nucleosomes and has been implicated in establishing a kinetochore-associated pool of Aurora B kinase, a chromosomal passenger complex (CPC) subunit, which is essential for chromosome biorientation.
Kinetochores are macromolecular protein complexes at centromeres that ensure accurate chromosome segregation by attaching chromosomes to spindle microtubules and integrating safeguard mechanisms.