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.
Dokumententyp: | Zeitschriftenartikel |
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EU Funded Grant Agreement Number: | 638218 |
EU-Projekte: | Horizon 2020 > ERC Grants > ERC Starting Grant > ERC Grant 638218: MolStruKT - Molecular structure and cell cycle regulated assembly of the kinetochore |
Fakultät: | Chemie und Pharmazie > Department Biochemie
Chemie und Pharmazie > GenZentrum |
Themengebiete: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
URN: | urn:nbn:de:bvb:19-epub-76115-5 |
Sprache: | Englisch |
Dokumenten ID: | 76115 |
Datum der Veröffentlichung auf Open Access LMU: | 01. Jun. 2021, 08:13 |
Letzte Änderungen: | 01. Jun. 2021, 08:13 |