Nature Cell Biology 8, 458 - 469 (2006)
Published online: 16 April 2006; | doi:10.1038/ncb1397
The human CENP-A centromeric nucleosome-associated complexDaniel R. Foltz1, 3, Lars E. T. Jansen1, 3, Ben E. Black1, 3, Aaron O. Bailey4, John R. Yates III4
& Don W. Cleveland1, 2, 31
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093–0670, USA. 2
Department of Medicine, University of California at San Diego, La Jolla, CA 92093–0670, USA. 3
Departments of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093–0670, USA. 4
The Scripps Research Institute, La Jolla, CA 92037, USA.
Correspondence should be addressed to Don W. Cleveland dcleveland@ucsd.edu 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.
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