CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold
Author(s)Nishino, Tatsuya; Takeuchi, Kozo; Gascoigne, Karen E.; Suzuki, Aussie; Hori, Tetsuya; Oyama, Takuji; Morikawa, Kosuke; Fukagawa, Tatsuo; Cheeseman, Iain McPherson; ... Show more Show less
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The multiprotein kinetochore complex must assemble at a specific site on each chromosome to achieve accurate chromosome segregation. Defining the nature of the DNA-protein interactions that specify the position of the kinetochore and provide a scaffold for kinetochore formation remain key goals. Here, we demonstrate that the centromeric histone-fold-containing CENP-T-W and CENP-S-X complexes coassemble to form a stable CENP-T-W-S-X heterotetramer. High-resolution structural analysis of the individual complexes and the heterotetramer reveals similarity to other histone fold-containing complexes including canonical histones within a nucleosome. The CENP-T-W-S-X heterotetramer binds to and supercoils DNA. Mutants designed to compromise heterotetramerization or the DNA-protein contacts around the heterotetramer strongly reduce the DNA binding and supercoiling activities in vitro and compromise kinetochore assembly in vivo. These data suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure to generate contacts with DNA, extending the “histone code” beyond canonical nucleosome proteins.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Nishino, Tatsuya, Kozo Takeuchi, Karen E. Gascoigne, Aussie Suzuki, Tetsuya Hori, Takuji Oyama, Kosuke Morikawa, Iain M. Cheeseman, and Tatsuo Fukagawa. “CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold.” Cell 148, no. 3 (February 2012): 487-501. Copyright © 2012 Elsevier Inc.
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