Induced Ectopic Kinetochore Assembly Bypasses the Requirement for CENP-A Nucleosomes
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Cheeseman_Induced ectopic.pdf
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Author(s)
Gascoigne, Karen E.
Takeuchi, Kozo
Suzuki, Aussie
Hori, Tetsuya
Fukagawa, Tatsuo
Cheeseman, Iain M
Date Issued
April 2011
Journal
Cell
Publisher
Elsevier
Citation
Gascoigne, Karen E., Kozo Takeuchi, Aussie Suzuki, Tetsuya Hori, Tatsuo Fukagawa, and Iain M. Cheeseman. “Induced Ectopic Kinetochore Assembly Bypasses the Requirement for CENP-A Nucleosomes.” Cell 145, no. 3 (April 2011): 410-422. Copyright © 2011 Elsevier Inc.
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Final published version
Abstract
Accurate chromosome segregation requires assembly of the multiprotein kinetochore complex at centromeres. Although prior work identified the centromeric histone H3-variant CENP-A as the important upstream factor necessary for centromere specification, in human cells CENP-A is not sufficient for kinetochore assembly. Here, we demonstrate that two constitutive DNA-binding kinetochore components, CENP-C and CENP-T, function to direct kinetochore formation. Replacing the DNA-binding regions of CENP-C and CENP-T with alternate chromosome-targeting domains recruits these proteins to ectopic loci, resulting in CENP-A-independent kinetochore assembly. These ectopic kinetochore-like foci are functional based on the stoichiometric assembly of multiple kinetochore components, including the microtubule-binding KMN network, the presence of microtubule attachments, the microtubule-sensitive recruitment of the spindle checkpoint protein Mad2, and the segregation behavior of foci-containing chromosomes. We additionally find that CENP-T phosphorylation regulates the mitotic assembly of both endogenous and ectopic kinetochores. Thus, CENP-C and CENP-T form a critical regulated platform for vertebrate kinetochore assembly.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.03.031
