CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold
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. Her...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/84581 https://orcid.org/0000-0002-3829-5612 |
| _version_ | 1811094532087873536 |
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| author | Nishino, Tatsuya Takeuchi, Kozo Gascoigne, Karen E. Suzuki, Aussie Hori, Tetsuya Oyama, Takuji Morikawa, Kosuke Fukagawa, Tatsuo Cheeseman, Iain M |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Nishino, Tatsuya Takeuchi, Kozo Gascoigne, Karen E. Suzuki, Aussie Hori, Tetsuya Oyama, Takuji Morikawa, Kosuke Fukagawa, Tatsuo Cheeseman, Iain M |
| author_sort | Nishino, Tatsuya |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:01:39Z |
| format | Article |
| id | mit-1721.1/84581 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:01:39Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/845812022-09-29T17:43:09Z CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold Nishino, Tatsuya Takeuchi, Kozo Gascoigne, Karen E. Suzuki, Aussie Hori, Tetsuya Oyama, Takuji Morikawa, Kosuke Fukagawa, Tatsuo Cheeseman, Iain M Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Gascoigne, Karen E. Cheeseman, Iain McPherson 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. Kinship Foundation. Searle Scholars Program National Institute of General Medical Sciences (U.S.) (Grant GM088313) 2014-01-27T17:22:03Z 2014-01-27T17:22:03Z 2012-02 2011-08 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/84581 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. https://orcid.org/0000-0002-3829-5612 en_US http://dx.doi.org/10.1016/j.cell.2011.11.061 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Nishino, Tatsuya Takeuchi, Kozo Gascoigne, Karen E. Suzuki, Aussie Hori, Tetsuya Oyama, Takuji Morikawa, Kosuke Fukagawa, Tatsuo Cheeseman, Iain M CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold |
| title | CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold |
| title_full | CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold |
| title_fullStr | CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold |
| title_full_unstemmed | CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold |
| title_short | CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold |
| title_sort | cenp t w s x forms a unique centromeric chromatin structure with a histone like fold |
| url | http://hdl.handle.net/1721.1/84581 https://orcid.org/0000-0002-3829-5612 |
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