The MIS12 Complex is a Protein Interaction Hub for Outer Kinetochore Assembly

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2010 Sep 8

PMID 20819937

Citations 139

Authors

Arsen Petrovic

Sebastiano Pasqualato

Prakash Dube

Veronica Krenn

Stefano Santaguida

Davide Cittaro

Silvia Monzani

Lucia Massimiliano

Jenny Keller

Aldo Tarricone

Alessio Maiolica

Holger Stark

Andrea Musacchio

Affiliations

Soon will be listed here.

Abstract

Kinetochores are nucleoprotein assemblies responsible for the attachment of chromosomes to spindle microtubules during mitosis. The KMN network, a crucial constituent of the outer kinetochore, creates an interface that connects microtubules to centromeric chromatin. The NDC80, MIS12, and KNL1 complexes form the core of the KMN network. We recently reported the structural organization of the human NDC80 complex. In this study, we extend our analysis to the human MIS12 complex and show that it has an elongated structure with a long axis of approximately 22 nm. Through biochemical analysis, cross-linking-based methods, and negative-stain electron microscopy, we investigated the reciprocal organization of the subunits of the MIS12 complex and their contacts with the rest of the KMN network. A highlight of our findings is the identification of the NSL1 subunit as a scaffold supporting interactions of the MIS12 complex with the NDC80 and KNL1 complexes. Our analysis has important implications for understanding kinetochore organization in different organisms.

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