TY - JOUR
T1 - Multiple assembly mechanisms anchor the KMN spindle checkpoint platform at human mitotic kinetochores
AU - Kim, Soonjoung
AU - Yu, Hongtao
N1 - Publisher Copyright:
© 2015 Kim and Yu.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201407074
DO - 10.1083/jcb.201407074
M3 - Article
C2 - 25601404
AN - SCOPUS:84921757340
SN - 0021-9525
VL - 208
SP - 181
EP - 196
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -