Multiple assembly mechanisms anchor the KMN spindle checkpoint platform at human mitotic kinetochores

Soonjoung Kim, Hongtao Yu

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

During mitosis, the spindle checkpoint senses kinetochores not properly attached to spindle microtubules and prevents precocious sisterchromatid separation and aneuploidy. The constitutive centromere-associated network (CCAN) at inner kinetochores anchors the KMN network consisting of Knl1, the Mis12 complex (Mis12C), and the Ndc80 complex (Ndc80C) at outer kinetochores. KMN is a critical kinetochore receptor for both microtubules and checkpoint proteins. Here, we show that nearly complete inactivation of KMN in human cells through multiple strategies produced strong checkpoint defects even when all kinetochores lacked microtubule attachment. These KMNinactivating strategies reveal multiple KMN assembly mechanisms at human mitotic kinetochores. In one mechanism, the centromeric kinase Aurora B phosphorylates Mis12C and strengthens its binding to the CCAN subunit CENP-C. In another, CENP-T contributes to KMN attachment in a CENP-H-I-K-dependent manner. Our study provides insights into the mechanisms of mitosisspecific assembly of the checkpoint platform KMN at human kinetochores.

Original languageEnglish (US)
Pages (from-to)181-196
Number of pages16
JournalJournal of Cell Biology
Volume208
Issue number2
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Multiple assembly mechanisms anchor the KMN spindle checkpoint platform at human mitotic kinetochores'. Together they form a unique fingerprint.

  • Cite this