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 similar to 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.

The MIS12 complex is a protein interaction hub for outer kinetochore assembly / A. Petrovic, S. Pasqualato, P. Dube, V. Krenn, S. Santaguida, D. Cittaro, S. Monzani, L. Massimiliano, J. Keller, A. Tarricone, A. Maiolica, H. Stark, A. Musacchio, S. RI santaguida stefano/G-2716-2010 Pasqualato. - In: THE JOURNAL OF CELL BIOLOGY. - ISSN 0021-9525. - 190:5(2010), pp. 835-852.

The MIS12 complex is a protein interaction hub for outer kinetochore assembly

S. Santaguida;
2010

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 similar to 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.
Microtubule attachment site; cenp-A nucleosomes; NDC80 complex; molecular architecture; yeast kinetochore; chromosome segregation; vertebrate kinetochore; mitotic checkpoint; aurora B; saccharomyces-cerevisiae
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/622932
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