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Free keywords:
CHROMOSOMAL PASSENGER COMPLEX; AURORA B KINASE; CENP-A NUCLEOSOMES;
CENTROMERIC NUCLEOSOME; MITOTIC CHECKPOINT; MOLECULAR-BASIS;
SACCHAROMYCES-CEREVISIAE; PROTEIN COMPLEX; RWD DOMAIN; SPINDLELife Sciences & Biomedicine - Other Topics;
Abstract:
Kinetochores are macromolecular protein complexes at centromeres that ensure accurate chromosome segregation by attaching chromosomes to spindle microtubules and integrating safeguard mechanisms. 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. 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 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. Tethering Sli15 to Ame1/Okp1 rescued synthetic lethality upon Ctf19 depletion in a Sli15 centromere-targeting deficient mutant. 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.
