CENP-C is a blueprint for constitutive centromere-associated network assembly within human kinetochores

Kerstin Klare, John R. Weir, Federica Basilico, Tomasz Zimniak, Lucia Massimiliano, Nina Ludwigs, Franz Herzog, Andrea Musacchio

Research output: Contribution to journalArticlepeer-review

Abstract

Kinetochores are multisubunit complexes that assemble on centromeres to bind spindle microtubules and promote faithful chromosome segregation during cell division. A 16-subunit complex named the constitutive centromere-associated network (CCAN) creates the centromere-kinetochore interface. CENP-C,a CCAN subunit, is crucial for kinetochore assembly because it links centromeres with the microtubule-binding interface of kinetochores. The role of CENP-C in CCAN organization, on the other hand, had been incompletely understood. In this paper, we combined biochemical reconstitution and cellular investigations to unveil how CENP-C promotes kinetochore targeting of other CCAN subunits. The so-called PEST domain in the N-terminal half of CENP-C interacted directly with the four-subunit CCAN subcomplexCENP-HIKM. We identified crucial determinants of this interaction whose mutation prevented kinetochore localization of CENP-HIKM and of CENP-TW, another CCAN subcomplex. When considered together with previous observations, our data point to CENP-C as a blueprint for kinetochore assembly.

Original languageEnglish
Pages (from-to)11-22
Number of pages12
JournalJournal of Cell Biology
Volume210
Issue number1
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Cell Biology

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