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Lookup NU author(s): Dr Lisa PrendergastORCiD
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© 2016 Nemajerova et al.The CENP-T/-W histone fold complex, as an integral part of the inner kinetochore, is essential for building a proper kinetochore at the centromere in order to direct chromosome segregation during mitosis. Notably, CENP-T/-W is not inherited at centromeres, and new deposition is absolutely required at each cell cycle for kinetochore function. However, the mechanisms underlying this new deposition of CENP-T/-W at centromeres are unclear. Here, we found that CENP-T deposition at centromeres is uncoupled from DNA synthesis. We identified Spt16 and SSRP1, subunits of the H2A–H2B histone chaperone facilitates chromatin transcription (FACT), as CENP-W binding partners through a proteomic screen. We found that the C-terminal region of Spt16 binds specifically to the histone fold region of CENP-T/-W. Furthermore, depletion of Spt16 impairs CENP-T and CENP-W deposition at endogenous centromeres, and site-directed targeting of Spt16 alone is sufficient to ensure local de novo CENP-T accumulation. We propose a model in which the FACT chaperone stabilizes the soluble CENP-T/-W complex in the cell and promotes dynamics of exchange, enabling CENP-T/-W deposition at centromeres.
Author(s): Prendergast L, Muller S, Liu Y, Huang H, Dingli F, Loew D, Vassias I, Patel DJ, Sullivan KF, Almouzni G
Publication type: Article
Publication status: Published
Journal: Genes and Development
Online publication date: 09/06/2016
Acceptance date: 02/05/2016
ISSN (print): 0890-9369
ISSN (electronic): 1549-5477
Publisher: Cold Spring Harbor Laboratory Press
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