The CENP-L-N Complex Forms a Critical Node in an Integrated Meshwork of Interactions at the Centromere-Kinetochore Interface
Name
The CENP-L-N Complex.pdf
Size
1.52 MB
Format
Adobe PDF
Checksum (MD5)
e38e19ed7a168f59b72aa0d2b6f8deed
Author(s)
Sekulic, Nikolina
Guo, Lucie Y.
Black, Ben E.
McKinley, Kara Lavidge
Tsinman, Tonia
Cheeseman, Iain M
Date Issued
November 2015
Journal
Molecular Cell
Publisher
Elsevier
Citation
McKinley, Kara L.; Sekulic, Nikolina; Guo, Lucie Y.; Tsinman, Tonia; Black, Ben E. and Cheeseman, Iain M. “The CENP-L-N Complex Forms a Critical Node in an Integrated Meshwork of Interactions at the Centromere-Kinetochore Interface.” Molecular Cell 60, no. 6 (December 2015): 886–898 © 2015 Elsevier Inc
Version
Author's final manuscript
Abstract
During mitosis, the macromolecular kinetochore complex assembles on the centromere to orchestrate chromosome segregation. The properties and architecture of the 16-subunit Constitutive Centromere-Associated Network (CCAN) that allow it to build a robust platform for kinetochore assembly are poorly understood. Here, we use inducible CRISPR knockouts and biochemical reconstitutions to define the interactions between the human CCAN proteins. We find that the CCAN does not assemble as a linear hierarchy, and instead, each sub-complex requires multiple non-redundant interactions for its localization to centromeres and the structural integrity of the overall assembly. We demonstrate that the CENP-L-N complex plays a crucial role at the core of this assembly through interactions with CENP-C and CENP-H-I-K-M. Finally, we show that the CCAN is remodeled over the cell cycle such that sub-complexes depend on their interactions differentially. Thus, an interdependent meshwork within the CCAN underlies the centromere specificity and stability of the kinetochore.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.molcel.2015.10.027
