Fischböck-Halwachs, Josef; Singh, Sylvia; Potocnjak, Mia; Hagemann, Götz; Solis-Mezarino, Victor; Woike, Stephan; Ghodgaonkar-Steger, Medini; Weissmann, Florian; Gallego, Laura D.; Rojas, Julie; Andreani, Jessica; Köhler, Alwin; Herzog, Franz  ORCID: 0000-0001-8270-1449
(2019):
The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore.
In: eLife, Vol. 8, e42879
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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/Okp1CENP-U/Q heterodimer, which forms the COMA complex with Ctf19/Mcm21CENP-P/O, selectively bound Cse4CENP-A nucleosomes through the Cse4 N-terminus. The Sli15/Ipl1INCENP/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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