Article abstract
Nature Cell Biology 8, 458 - 469 (2006)
Published online: 16 April 2006 | doi:10.1038/ncb1397
The human CENP-A centromeric nucleosome-associated complex
Daniel R. Foltz1,3, Lars E. T. Jansen1,3, Ben E. Black1,3, Aaron O. Bailey4, John R. Yates, III4 & Don W. Cleveland1,2,3
Abstract
The basic element for chromosome inheritance, the centromere, is epigenetically determined in mammals. The prime candidate for specifying centromere identity is the array of nucleosomes assembled with CENP-A, the centromere-specific histone H3 variant. Here, we show that CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of three new human centromere proteins (CENP-M, CENP-N and CENP-T), along with CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Facilitates chromatin transcription (FACT) and nucleophosmin-1 (previously implicated in transcriptional chromatin remodelling and as a multifunctional nuclear chaperone, respectively) are absent from histone H3-containing nucleosomes, but are stably recruited to CENP-A nucleosomes independent of CENP-A NAC. Seven new CENP-A-nucleosome distal (CAD) centromere components (CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S) are identified as assembling on the CENP-A NAC. The CENP-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival despite continued centromere-derived mitotic checkpoint signalling.
- Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093–0670, USA.
- Department of Medicine, University of California at San Diego, La Jolla, CA 92093–0670, USA.
- Departments of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093–0670, USA.
- The Scripps Research Institute, La Jolla, CA 92037, USA.
Correspondence to: Don W. Cleveland1,2,3 e-mail: dcleveland@ucsd.edu
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