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.

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Journal Article | Research Support, Non-U.S. Gov't

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Fischböck-Halwachs J, Singh S, Potocnjak M, Hagemann G, Solis-Mezarino V, Woike S, Ghodgaonkar-Steger M, Weissmann F, Gallego LD, Rojas J, ... Show all

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