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J Cell Biol. 2019 Jul 1;218(7):2124-2135. doi: 10.1083/jcb.201810070. Epub 2019 May 22.

The stoichiometry of the outer kinetochore is modulated by microtubule-proximal regulatory factors.

Author information

1
Stowers Institute for Medical Research, Kansas City, MO.
2
Open University, Milton Keynes, England, UK.
3
Stowers Institute for Medical Research, Kansas City, MO jeg@stowers.org.
4
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS.

Abstract

The kinetochore is a large molecular machine that attaches chromosomes to microtubules and facilitates chromosome segregation. The kinetochore includes submodules that associate with the centromeric DNA and submodules that attach to microtubules. Additional copies of several submodules of the kinetochore are added during anaphase, including the microtubule binding module Ndc80. While the factors governing plasticity are not known, they could include regulation based on microtubule-kinetochore interactions. We report that Fin1 localizes to the microtubule-proximal edge of the kinetochore cluster during anaphase based on single-particle averaging of super-resolution images. Fin1 is required for the assembly of normal levels of Dam1 and Ndc80 submodules. Levels of Ndc80 further depend on the Dam1 microtubule binding complex. Our results suggest the stoichiometry of outer kinetochore submodules is strongly influenced by factors at the kinetochore-microtubule interface such as Fin1 and Dam1, and phosphorylation by cyclin-dependent kinase. Outer kinetochore stoichiometry is remarkably plastic and responsive to microtubule-proximal regulation.

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