Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore

Emanuela Screpanti, Anna De Antoni, Gregory M. Alushin, Arsen Petrovic, Tiziana Melis, Eva Nogales, Andrea Musacchio

Research output: Contribution to journalArticle


Kinetochores are proteinaceous scaffolds implicated in the formation of load-bearing attachments of chromosomes to microtubules during mitosis. Kinetochores contain distinct chromatin- and microtubule-binding interfaces, generally defined as the inner and outer kinetochore, respectively (reviewed in [1]). The constitutive centromere-associated network (CCAN) and the Knl1-Mis12-Ndc80 complexes (KMN) network are the main multisubunit protein assemblies in the inner and outer kinetochore, respectively. The point of contact between the CCAN and the KMN network is unknown. Cenp-C is a conserved CCAN component whose central and C-terminal regions have been implicated in chromatin binding and dimerization [2-10]. Here, we show that a conserved motif in the N-terminal region of Cenp-C binds directly and with high affinity to the Mis12 complex. Expression in HeLa cells of the isolated N-terminal motif of Cenp-C prevents outer kinetochore assembly, causing chromosome missegregation. The KMN network is also responsible for kinetochore recruitment of the components of the spindle assembly checkpoint, and we observe checkpoint impairment in cells expressing the Cenp-C N-terminal segment. Our studies unveil a crucial and likely universal link between the inner and outer kinetochore.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalCurrent Biology
Issue number5
Publication statusPublished - Mar 8 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Screpanti, E., De Antoni, A., Alushin, G. M., Petrovic, A., Melis, T., Nogales, E., & Musacchio, A. (2011). Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore. Current Biology, 21(5), 391-398.